1: J Mol Neurosci. 2005;27(3):281-92. Phox2 and dHAND Transcription Factors Select Shared and Unique Target Genes in the Noradrenergic Cell Type. Rychlik JL, Hsieh M, Eiden LE, Lewis EJ. Department of Biochemistry and Molecular Biology, Oregon Health and Sciences University, Portland, OR. The noradrenergic cell type is characterized by the expression of proteins involved in the biosynthesis, transport, and secretion of noradrenaline and is dependent on the sequential and combinatorial expression of numerous transcription factors, including Phox2a, Phox2b, dHAND, GATA2, GATA3, and MASH1. Phox2a and Phox2b transactivate the promoter of the gene encoding the noradrenergic biosynthetic enzyme, dopamine beta-hydroxylase (DBH), and dHAND potentiates the activity of Phox2a. In this study, we use chromatin immunoprecipitation assays to identify target genes of the Phox2 proteins and dHAND. All three proteins are bound to the DBH and PHOX2B promoter regions in SH-SY5Y neuroblastoma cells. The interaction between Phox2a and dHAND is analyzed by fluorescent anisotropy, which demonstrates that dHAND causes an eightfold increase in the affinity of Phox2a for its recognition sites on the DBH promoter region. The Phox2 proteins are not found on the genes encoding other noradrenergic enzymatic or transport proteins but are reciprocally bound to each other's promoters in SH-SY5Y cells. Together with Phox2a and Phox2b, dHAND is bound to the PHOX2B promoter and is also associated with the GATA2 and eHAND genes in the absence of the Phox2 proteins. These results demonstrate the direct interactions of the Phox2 and dHAND transcription factors within a noradrenergic cell type. The Phox2 proteins were found to share all target genes, whereas dHAND binds to genes independently of Phox2a. PMID: 16280598 [PubMed - in process] --------------------------------------------------------------- 2: Mol Genet Metab. 2005 Jun;85(2):140-8. Study of a new PPARgamma2 promoter polymorphism and haplotype analysis in a French population. Meirhaeghe A, Tanck MW, Fajas L, Janot C, Helbecque N, Cottel D, Auwerx J, Amouyel P, Dallongeville J. INSERM, U508, Institut Pasteur de Lille, 1 rue du Pr. Calmette, BP 245, Lille Cedex F-59019, France. Aline.Meirhaeghe-Hurez@pasteur-lille.fr Peroxisome proliferator-activated receptor-gamma (PPARgamma) plays a role in adipocyte differentiation and insulin sensitization. We identified and characterized a new C/T substitution at position -689 (-689C>T) in the P2 promoter of PPARgamma in a putative GATA binding site. By electrophoretic mobility shift assay, both GATA2 and GATA3 proteins could bind weakly to the wild-type P2 -689 GATA binding site but not to the mutated site. Neither GATA2 nor GATA3 was able to regulate significantly the P2 promoter activity in a reporter-luciferase assay, whatever the allele at position -689 was, suggesting that the -689 putative GATA site was probably not a functional target for GATAs. However, the presence of the -689T allele rendered the P2 promoter less active at the basal state. We genotyped a population of 1155 men and women for the -689C>T polymorphism and looked for possible associations with anthropometric and lipid variables. The carriers of the -689T allele had elevated body weight and LDL-cholesterol concentrations compared with the homozygous for the common allele. Haplotype analyses including the -681C>G (P3 promoter), -689C>T (P2 promoter), and Pro12Ala (exon B) polymorphisms were performed. Carriers of the G-T-Ala haplotype (corresponding to the P3 -681C>G, P2 -689C>T and Pro12Ala polymorphisms in this order) had elevated LDL-cholesterol concentrations and body weight compared with C-C-Pro individuals. In conclusion, we identified a new polymorphism in the P2 promoter of PPARgamma. The P3 -681C>G, P2 -689C>T, and Pro12Ala polymorphisms and related haplotypes were associated with higher body weight and plasma LDL-cholesterol concentrations. PMID: 15896659 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 3: Biol Reprod. 2005 Sep;73(3):500-9. Epub 2005 May 11. A placenta-specific enhancer of the human syncytin gene. Cheng YH, Handwerger S. Department of Pediatrics, University of Cincinnati College of Medicine and Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA. The cis- and trans-acting factors that are critical for placenta-specific expression of the human syncytin gene are unknown. We identified a 146-base pair (bp) region of the 5'-flanking region of the human syncytin gene from nt-294 to -148 that is essential for basal gene expression in human BeWo and JEG3 choriocarcinoma cell lines but not in hepatoblastoma and kidney cell lines. Ligation of the 146-bp fragment to a SV40 promoter or a human beta-globin minimal promoter markedly enhanced promoter activity in the placenta cells but not in the liver and kidney cells. DNase I footprint assays indicated that nuclear extracts from BeWo cells but not HepG2 cells protected four regions (FP1-FP4) of the 146-bp fragment. Site-directed mutagenesis of an SP1-binding site in FP3 and a GATA-binding site in FP4 significantly repressed promoter activity in the placenta cells. Overexpression of SP1 (Sp1 transcription factor) and GATA2 (GATA binding protein 2) and GATA3 induced syncytin promoter activity but had little or no effect on the activities of syncytin promoter fragments containing mutations in the SP1- and GATA-binding sites. GATA2 and -3 mRNA levels increased markedly during spontaneous in vitro differentiation of human cytotrophoblast cells when the cytotrophoblast cells fused to form a syncytium. These findings strongly suggest that the 146-bp region of the 5'-flanking region (nt-294/-148) of the human syncytin gene acts as a placenta-specific enhancer. Binding of SP1 and GATA family members to this enhancer is critical for cell-specific expression of the syncytin gene. PMID: 15888734 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 4: Semin Cell Dev Biol. 2005 Feb;16(1):95-106. Epub 2004 Dec 10. Using the zebrafish model to study GATA transcription factors. Heicklen-Klein A, McReynolds LJ, Evans T. Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Chanin Room 501, Bronx, NY 10461, USA. The zebrafish is an established animal model system that profits from the availability of strong experimental approaches in both genetics and embryology. As a vertebrate, zebrafish can be used to model many aspects of human development and disease. GATA transcription factors play important roles in the development of many organ systems, including those for hematopoietic, cardiovascular, reproductive, and gut-endoderm derived tissues. The six vertebrate GATA factors are highly conserved in zebrafish at the level of sequence, expression pattern, and function. The identification of mutants, establishment of transgenic GFP reporter fish, and the ease of performing loss- and gain-of-function experiments have all contributed new insight into our understanding of the regulation and function of GATA factors. We review recent advances toward this goal using the zebrafish system with a focus on hematopoiesis and cardiogenesis, and suggest how comparative genetics using the zebrafish genes might reveal core conserved properties, as well as changes in gene function that reflect different morphogenetic programs utilized by various vertebrate embryos. Publication Types: Review Review, Tutorial PMID: 15659344 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 5: Semin Cell Dev Biol. 2005 Feb;16(1):71-81. Epub 2004 Dec 10. Regulation of GATA gene expression during vertebrate development. Burch JB. Cell and Developmental Biology Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA. john.burch@fccc.edu GATA factors regulate critical events in hematopoietic lineages (GATA-1/2/3), the heart and gut (GATA-4/5/6) and various other tissues. Transgenic approaches have revealed that GATA genes are regulated in a modular fashion by sets of enhancers that govern distinct temporal and/or spatial facets of the overall expression patterns. Efforts are underway to resolve how these GATA gene enhancers are themselves regulated in order to elucidate the genetic and molecular hierarchies that govern GATA expression in particular developmental contexts. These enhancers also afford a raft of tools that can be used to selectively perturb and probe various developmental events in transgenic animals. Publication Types: Review Review, Tutorial PMID: 15659342 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 6: Mol Cell Biol. 2005 Jan;25(2):706-15. Interaction between GATA and the C/EBP family of transcription factors is critical in GATA-mediated suppression of adipocyte differentiation. Tong Q, Tsai J, Tan G, Dalgin G, Hotamisligil GS. Department of Genetics and Complex Diseases, Harvard School of Public Health, 665 Huntington Ave., Bldg. 1, Rm. 207, Boston, MA 02115, USA. We have previously demonstrated that GATA-2 and GATA-3 are expressed in adipocyte precursors and control the preadipocyte-to-adipocyte transition. Constitutive expression of both GATA-2 and GATA-3 suppressed adipocyte differentiation, partially through direct binding to the peroxisome proliferator-activated receptor gamma (PPARgamma) promoter and suppression of its basal activity. In the present study, we demonstrate that both GATA-2 and GATA-3 form protein complexes with CCAAT/enhancer binding protein alpha (C/EBPalpha) and C/EBPbeta, members of a family of transcription factors that are integral to adipogenesis. We mapped this interaction to the basic leucine zipper domain of C/EBPalpha and a region adjacent to the carboxyl zinc finger of GATA-2. The interaction between GATA and C/EBP factors is critical for the ability of GATA to suppress adipocyte differentiation. Thus, these results show that in addition to its previously recognized function in suppressing PPARgamma transcriptional activity, interaction of GATA factors with C/EBP is necessary for their ability to negatively regulate adipogenesis. PMID: 15632071 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 7: Dev Dyn. 2005 Feb;232(2):487-97. Vascular gene expression and phenotypic correlation during differentiation of human embryonic stem cells. Gerecht-Nir S, Dazard JE, Golan-Mashiach M, Osenberg S, Botvinnik A, Amariglio N, Domany E, Rechavi G, Givol D, Itskovitz-Eldor J. Department of Obstetrics and Gynecology, Rambam Medical Center, Haifa 31096, Israel. The study of the cascade of events of induction and sequential gene activation that takes place during human embryonic development is hindered by the unavailability of postimplantation embryos at different stages of development. Spontaneous differentiation of human embryonic stem cells (hESCs) can occur by means of the formation of embryoid bodies (EBs), which resemble certain aspects of early embryos to some extent. Embryonic vascular formation, vasculogenesis, is a sequential process that involves complex regulatory cascades. In this study, changes of gene expression along the development of human EBs for 4 weeks were studied by large-scale gene screening. Two main clusters were identified-one of down-regulated genes such as POU5, NANOG, TDGF1/Cripto (TDGF, teratocarcinoma-derived growth factor-1), LIN28, CD24, TERF1 (telomeric repeat binding factor-1), LEFTB (left-right determination, factor B), and a second of up-regulated genes such as TWIST, WNT5A, WT1, AFP, ALB, NCAM1. Focusing on the vascular system development, genes known to be involved in vasculogenesis and angiogenesis were explored. Up-regulated genes include vasculogenic growth factors such as VEGFA, VEGFC, FIGF (VEGFD), ANG1, ANG2, TGFbeta3, and PDGFB, as well as the related receptors FLT1, FLT4, PDGFRB, TGFbetaR2, and TGFbetaR3, other markers such as CD34, VCAM1, PECAM1, VE-CAD, and transcription factors TAL1, GATA2, and GATA3. The reproducibility of the array data was verified independently and illustrated that many genes known to be involved in vascular development are activated during the differentiation of hESCs in culture. Hence, the analysis of the vascular system can be extended to other differentiation pathways, allocating human EBs as an in vitro model to study early human development. Copyright 2004 Wiley-Liss, Inc. PMID: 15614775 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 8: Dev Dyn. 2004 Dec;231(4):775-81. Partially overlapping expression of Gata2 and Gata3 during inner ear development. Lillevali K, Matilainen T, Karis A, Salminen M. Institute of Biotechnology, University of Helsinki, Helsinki, Finland. Gata2 and Gata3 belong to the Gata family of transcription factors in vertebrates that bind to a consensus "GATA" DNA sequence. The Gata3 gene is one of the earliest markers for the developing mouse inner ear. Ear morphogenesis is blocked in Gata3-deficient embryos, whereas nothing was known of the role of Gata2 in mouse inner ear. Here, we have compared the expression patterns of Gata2 and Gata3 during normal inner ear development and investigated their relationship in mice where either Gata3 or Gata2 has been inactivated. The expression of the two Gata genes is highly overlapping at embryonic day (E)10.5 but becomes increasingly distinct later. Whereas Gata2 is predominantly expressed in the dorsal vestibular system, Gata3 was detected mainly in the ventral cochlear duct and ganglion. No phenotypic abnormalities were observed in the inner ear of Gata2-/- embryos before lethality at E10.5 and Gata3 expression was unchanged. In contrast, a delay and strong reduction of Gata2 expression was detected in Gata3-/- otic epithelium. Copyright (c) 2004 Wiley-Liss, Inc. PMID: 15499560 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 9: J Immunol. 2004 Nov 1;173(9):5564-73. The interaction between GATA proteins and activator protein-1 promotes the transcription of IL-13 in mast cells. Masuda A, Yoshikai Y, Kume H, Matsuguchi T. Division of Host Defense, Center for Neural Disease and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan. amasuda@med.nagoya-u.ac.jp IL-13 is considered to be a key modulator in the pathogenesis of Th2-induced allergic inflammation, although little is known about the regulation of IL-13 transcription in mast cells. In T cells, involvement of GATA-3 in cell type-specific expression of the IL-13 gene has been reported. However, the mechanisms that induce rapid transactivation of the IL-13 gene in response to various types of stimulation have hitherto remained unknown. In this report, we describe our investigation of the promoter region necessary for IL-13 transcription; we have found that both AP-1 and GATA proteins are indispensable for IL-13 transcription in mouse mast cells. In our investigation, we focused on the functional interaction between GATA and AP-1 in the IL-13 promoter context. Transfection experiments have revealed that GATA-1 and GATA-2 proteins are able to associate with AP-1 proteins. We have also shown that overexpression of GATA-1 induced excess AP-1 binding to the IL-13 promoter as well as a significant increase in IL-13 production in mast cells. The results of the present study have shown that direct interaction between AP-1 and GATA proteins plays an important role in IL-13 transcription in mast cells. PMID: 15494506 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 10: J Immunol. 2004 Oct 15;173(8):4967-75. STAT6-dependent differentiation and production of IL-5 and IL-13 in murine NK2 cells. Katsumoto T, Kimura M, Yamashita M, Hosokawa H, Hashimoto K, Hasegawa A, Omori M, Miyamoto T, Taniguchi M, Nakayama T. Department of Immunology, Graduate School of Medicine, Chiba University, Inohana, Chuo-ku, Japan. NK cells differentiate into either NK1 or NK2 cells that produce IFN-gamma or IL-5 and IL-13, respectively. Little is known, however, about the molecular mechanisms that control NK1 and NK2 cell differentiation. To address these questions, we established an in vitro mouse NK1/NK2 cell differentiation culture system. For NK1/NK2 cell differentiation, initial stimulation with PMA and ionomycin was required. The in vitro differentiated NK2 cells produced IL-5 and IL-13, but the levels were 20 times lower than those of Th2 or T cytotoxic (Tc)2 cells. No detectable IL-4 was produced. Freshly prepared NK cells express IL-2Rbeta, IL-2RgammaC, and IL-4Ralpha. After stimulation with PMA and ionomycin, NK cells expressed IL-2Ralpha. NK1 cells displayed higher cytotoxic activity against Yac-1 target cells. The levels of GATA3 protein in developing NK2 cells were approximately one-sixth of those in Th2 cells. Both NK1 and NK2 cells expressed large amounts of repressor of GATA, the levels of which were equivalent to CD8 Tc1 and Tc2 cells and significantly higher than those in Th2 cells. The levels of histone hyperacetylation of the IL-4 and IL-13 gene loci in NK2 cells were very low and equivalent to those in naive CD4 T cells. The production of IL-5 and IL-13 in NK2 cells was found to be STAT6 dependent. Thus, similar to Th2 cells, NK2 cell development is dependent on STAT6, and the low level expression of GATA3 and the high level expression of repressor of GATA may influence the unique type 2 cytokine production profiles of NK2 cells. PMID: 15470039 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 11: Leuk Res. 2004 Nov;28(11):1227-37. Analysis of the relationship between Scl transcription factor complex protein expression patterns and the effects of LiCl on ATRA-induced differentiation in blast cells from patients with acute myeloid leukemia. Rice AM, Holtz KM, Karp J, Rollins S, Sartorelli AC. Department of Pharmacology, Cancer Center, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA. Exogenous expression of the transcription factor Scl (Tal1) in WEHI-3B D+ myelomonocytic leukemia cells interferes with their capacity to respond to all-trans retinoic acid (ATRA) induced differentiation; combination of ATRA with LiCl, however, circumvents the inhibition of differentiation produced by Scl. To gain information on the possible involvement of this transcription factor in the non-responsiveness of acute myelocytic leukemia (AML) patients to ATRA, we compared the endogenous expression levels of Scl and its transcription complex partners [i.e., Rbtn1 (LMO1), Rbtn2 (LMO2), Ldb1, and GATA family proteins] in leukemic blast cells from patients with AML and acute promyelocytic leukemia (APL), and determined the effects of lithium chloride alone or in combination with ATRA on the capacity of blast cells to differentiate during short-term ex vivo culture. Levels of Scl, Rbtn2, GATA1, and Ldb1 expression were comparable in AML and APL blasts, while the levels of expression of Rbtn1, GATA2, and GATA3 were absent or markedly lower in APL cells. Differentiation markers (cell surface myeloid antigens CD11b, CD15, CD14, and CD33) were also analyzed in blast cells. ATRA produced changes in at least one surface antigen differentiation marker in 89% of patient blasts, while LiCl caused such changes in 72% of the leukemic cells of patients. The combination of LiCl and ATRA induced the differentiation of leukemic blasts from 94% of patients. Although the expression of the transcription factors did not act as individual predictors of responsiveness or non-responsiveness to the inducers of differentiation, ATRA or ATRA plus LiCl, the addition of LiCl to ATRA increased the differentiation response over that of ATRA alone in a number of leukemic samples. These findings suggest that the combination of LiCl and ATRA may produce some clinical benefit in the treatment of the myeloid leukemias. PMID: 15380350 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 12: Hum Cell. 2004 Jun;17(2):85-92. Transcription factor expression in cell lines derived from natural killer-cell and natural killer-like T-cell leukemia-lymphoma. Matsuo Y, Drexler HG, Harashima A, Okochi A, Shimizu N, Orita K. Fujisaki Cell Center, Hayashibara Biochemical Labs, Okayama 702-8006, Japan. yomatsuo@hayashibara.co.jp Although a number of transcription factors (TFs) have been identified that play a pivotal role in the development of hematopoietic lineages, only little is known about factors that may influence development and lineage commitment of natural killer (NK) or NK-like T (NKT)-cells. Obviously to fully appreciate the NK- and NKT-cell differentiation process, it is important to identify and characterize the TFs effecting the NK- and NKT-cell lineage. Furthermore, these TFs may play a role in NK- or NKT-cell leukemias, in which the normal differentiation program is presumably disturbed. The present study analyzed the expression of the following 13 TFs: AML1, CEBPA, E2A, ETS1, GATA1, GATA2, GATA3, IKAROS, IRF1, PAX5, PU1, TBET and TCF1 in 7 malignant NK-cell lines together with 5 malignant NKT-cell lines, 5 T-cell acute lymphoblastic leukemia (ALL) cell lines including 3 gamma/delta T-cell receptor (TCR) type and 2 alpha/beta TCR type, and 3 B-cell precursor (BCP) leukemia cell lines. AML1, E2A, ETS1, IKAROS and IRF1 were found to be positive for all cell lines tested whereas GATA1 turned out to be universally negative. CEBPA, PAX5 and PU1 were negative for all cell lines tested except in the three positive BCP-cell lines. GATA2 was positive for 3/5 T-cell lines but negative for the other cell lines. GATA3 was positive for 7/7 NK-, 4/5 NKT-, 5/5 T- and 2/3 BCP-cell lines. TBET was positive for all NK- and NKT-cell lines and negative for all T- and BCP-cell lines except one BCP-cell line. In contrast to the expression of TBET, TCF1 was negative for all NK- and NKT-cell lines, being positive for 4/5 T- and 1/3 BCP-cell lines. Expression analysis of TFs revealed that NK- and NKT-cell lines showed identical profiles, clearly distinct from those of the other T-ALL or BCP-ALL leukemia-derived cell lines.. PMID: 15369140 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 13: Development. 2004 Oct;131(19):4775-86. Epub 2004 Aug 25. Essential role of Gata transcription factors in sympathetic neuron development. Tsarovina K, Pattyn A, Stubbusch J, Muller F, van der Wees J, Schneider C, Brunet JF, Rohrer H. Max-Planck-Institut fur Hirnforschung, Abteilung Neurochemie, Deutschordenstr. 46, 60528 Frankfurt/Main, Germany. Sympathetic neurons are specified during their development from neural crest precursors by a network of crossregulatory transcription factors, which includes Mash1, Phox2b, Hand2 and Phox2a. Here, we have studied the function of Gata2 and Gata3 zinc-finger transcription factors in autonomic neuron development. In the chick, Gata2 but not Gata3 is expressed in developing sympathetic precursor cells. Gata2 expression starts after Mash1, Phox2b, Hand2 and Phox2a expression, but before the onset of the noradrenergic marker genes Th and Dbh, and is maintained throughout development. Gata2 expression is affected in the chick embryo by Bmp gain- and loss-of-function experiments, and by overexpression of Phox2b, Phox2a, Hand2 and Mash1. Together with the lack of Gata2/3 expression in Phox2b knockout mice, these results characterize Gata2 as member of the Bmp-induced cluster of transcription factors. Loss-of-function experiments resulted in a strong reduction in the size of the sympathetic chain and in decreased Th expression. Ectopic expression of Gata2 in chick neural crest precursors elicited the generation of neurons with a non-autonomic, Th-negative phenotype. This implies a function for Gata factors in autonomic neuron differentiation, which, however, depends on co-regulators present in the sympathetic lineage. The present data establish Gata2 and Gata3 in the chick and mouse, respectively, as essential members of the transcription factor network controlling sympathetic neuron development. PMID: 15329349 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 14: Blood. 2004 Dec 15;104(13):4300-7. Epub 2004 Aug 24. Oral administration of K-11706 inhibits GATA binding activity, enhances hypoxia-inducible factor 1 binding activity, and restores indicators in an in vivo mouse model of anemia of chronic disease. Nakano Y, Imagawa S, Matsumoto K, Stockmann C, Obara N, Suzuki N, Doi T, Kodama T, Takahashi S, Nagasawa T, Yamamoto M. Division of Hematology, Institute of Clinical Medicine, Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan. Erythropoietin (Epo) gene expression is under the control of hypoxia-inducible factor 1 (HIF-1), and is negatively regulated by GATA. Interleukin 1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha), which increase the binding activity of GATA and inhibit Epo promoter activity, are increased in patients with anemia of chronic disease (ACD). We previously demonstrated the ability of K-7174 (a GATA-specific inhibitor), when injected intraperitoneally, to improve Epo production that had been inhibited by IL-1beta or TNF-alpha treatment. In the present study, we examined the ability of both K-11706, which inhibits GATA and enhances HIF-1 binding activity, and K-13144, which has no effect on GATA or HIF-1 binding activity, to improve Epo production following inhibition by IL-1beta or TNF-alpha in Hep3B cells in vitro and in an in vivo mouse assay. Oral administration of K-11706 reversed the decreases in hemoglobin and serum Epo concentrations, reticulocyte counts, and numbers of erythroid colony-forming units (CFU-Es) induced by IL-1beta or TNF-alpha. These results raise the possibility of using orally administered K-11706 for treating patients with ACD. PMID: 15328158 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 15: Dev Comp Immunol. 2004 Aug;28(10):993-1003. Transcriptome analysis of hagfish leukocytes: a framework for understanding the immune system of jawless fishes. Suzuki T, Shin-I T, Kohara Y, Kasahara M. Department of Biosystems Science, School of Advanced Sciences, The Graduate University for Advanced Studies (Sokendai), Shonan Village, Hayama 240-0193, Japan. Jawless fishes occupy a critical phylogenetic position in understanding the origin of the adaptive immune system. Here, we performed large-scale expressed sequence tag analysis of leukocytes isolated from the inshore hagfish Eptatretus burgeri. Although we found many immunity-related genes such as those involved in lymphocyte or hematopoietic cell signaling and development as well as cytokine and cytokine receptor genes, MHC molecules or antigen receptors were not identified. We characterized two hagfish cDNAs that closely resembled mammalian proteins with essential roles in adaptive immunity, one encoding a GATA3-like molecule and another encoding a Bruton's tyrosine kinase (Btk)-like molecule. The GATA3-like gene of hagfish was equidistant from GATA3 and GATA2 in jawed vertebrates. Similarly, the hagfish Btk-like molecule was not Btk itself, but qualified as a pre-duplicated form of Btk and Bmx in jawed vertebrates. In total, our work provides circumstantial evidence that adaptive immunity is unique to jawed vertebrates. PMID: 15236930 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 16: Development. 2004 Mar;131(5):1165-73. Gata2 specifies serotonergic neurons downstream of sonic hedgehog. Craven SE, Lim KC, Ye W, Engel JD, de Sauvage F, Rosenthal A. Department of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA. craven@gene.com Distinct classes of serotonergic (5-HT) neurons develop along the ventral midline of the vertebrate hindbrain. Here, we identify a Sonic hedgehog (Shh)-regulated cascade of transcription factors that acts to generate a specific subset of 5-HT neurons. This transcriptional cascade is sufficient for the induction of rostral 5-HT neurons within rhombomere 1 (r1), which project to the forebrain, but not for the induction of caudal 5-HT neurons, which largely terminate in the spinal cord. Within the rostral hindbrain, the Shh-activated homeodomain proteins Nkx2.2 and Nkx6.1 cooperate to induce the closely related zinc-finger transcription factors Gata2 and Gata3. Gata2 in turn is necessary and sufficient to activate the transcription factors Lmx1b and Pet1, and to induce 5-HT neurons within r1. In contrast to Gata2, Gata3 is not required for the specification of rostral 5-HT neurons and appears unable to substitute for the loss of Gata2. Our findings reveal that the identity of closely related 5-HT subclasses occurs through distinct responses of adjacent rostrocaudal progenitor domains to broad ventral inducers. PMID: 14973276 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 17: Drug News Perspect. 2003 Nov;16(9):585-8. GATA transcription factors and fat cell formation. Tong Q, Tsai J, Hotamisligil GS. Department of Pediatrics, ARS/Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas, USA. ghotamis@hsph.harvard.edu GATA transcription factors play important roles in a variety of developmental processes. Recently, we discovered that GATA factors also play a key role in adipogenesis. Two isoforms, GATA-2 and GATA-3, are specifically expressed in murine preadipocytes but not mature adipocytes. Continuous expression of GATA factors in preadipocyte cell lines inhibits terminal differentiation into mature adipocytes. In contrast, GATA-3-deficient mouse embryonic stem cells possess a higher capacity to convert to adipocytes. The inhibitory effect of GATA on adipogenesis is mediated in part by suppression of promoters of adipogenic factors, including peroxisome proliferator-activated receptor gamma, but additional mechanisms are also likely to be in effect. These findings indicate that GATA factors function as molecular gatekeepers at the onset of terminal adipocyte differentiation. Whether GATA factors are also involved in the commitment of multipotent mesenchymal stem cells to progenitors of the adipogenic lineage is under investigation. Publication Types: Review Review, Tutorial PMID: 14702139 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 18: Blood. 2004 May 1;103(9):3320-5. Epub 2003 Dec 30. Essential role of HGF (hepatocyte growth factor) in blood formation in Xenopus. Koibuchi N, Kaneda Y, Taniyama Y, Matsumoto K, Nakamura T, Ogihara T, Morishita R. Division of Gene Therapy, Graduate School of Medicine, Osaka University, Suita, Japan. In this study, we investigated the role of hepatocyte growth factor (HGF) in blood formation during Xenopus development. First, we examined the gene expression of HGF and its receptor, c-met, by whole-mount in situ hybridization during development. Strong signals of HGF as well as c-met were detected early in the developing ventral mesoderm, which later gives rise to the ventral blood island. Furthermore, to study the role of HGF, we blocked the HGF signaling pathway in Xenopus embryos by using truncated c-met lacking the tyrosine kinase domain. Injection of truncated c-met mRNA resulted in a marked decrease in the number of circulating blood cells. Similar results were obtained using morpholino antisense HGF oligonucleotides. Moreover, we also analyzed the expression of several early primitive blood markers in the blood island of these embryos. RNA in situ analysis revealed a significant reduction (or absence) of stem cell leukemia (SCL), alpha-globin, and GATA-1 expression, but not GATA-2 expression. In contrast, no significant difference was observed in the levels of expression of early definitive blood markers, SCL, GATA-2, and GATA-3 in the dorsolateral plate, as analyzed by in situ hybridization. Overall, the present study demonstrated that HGF is necessary for primitive hematopoiesis by regulating the expression of SCL. PMID: 14701703 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 19: J Biol Chem. 2004 Jan 23;279(4):2955-61. Epub 2003 Oct 28. Hepatic erythropoietin gene regulation by GATA-4. Dame C, Sola MC, Lim KC, Leach KM, Fandrey J, Ma Y, Knopfle G, Engel JD, Bungert J. Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, Florida 32610, USA. Erythropoietin production switches from fetal liver to adult kidney during development. GATA transcription factors 2 and 3 could be involved in modulating this switch, because they were shown to negatively regulate erythropoietin gene transcription through a promoter proximal GATA site. Herein, we analyzed the role of several GATA factors in the regulation of the erythropoietin gene in human liver and in hepatoma cells. Although GATA-3 expression in hepatocytes increases during human development, erythropoietin mRNA accumulation is unaltered in mutant mice lacking GATA-3. We found that GATA-2, -3, -4, and -6 are all expressed in human hepatocytes and that GATA-4 exhibits the most prominent Epo promoter binding activity in vitro and in vivo. Inhibition of GATA-4 expression by RNA interference leads to a dramatic reduction in Epo gene transcription in Hep3B cells. Moreover, GATA-4 expression is high and limited to hepatocytes in the fetal liver, whereas GATA-4 expression in the adult liver is low and restricted to epithelial cells surrounding the biliary ducts. Thus, GATA-4 is critical for transcription of the Epo gene in hepatocytes and may contribute to the switch in the site of Epo gene expression from the fetal liver to the adult kidney. PMID: 14583613 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 20: EMBO J. 2003 Aug 1;22(15):3887-97. Myeloid lineage switch of Pax5 mutant but not wild-type B cell progenitors by C/EBPalpha and GATA factors. Heavey B, Charalambous C, Cobaleda C, Busslinger M. Research Institute of Molecular Pathology, Vienna Biocenter,Dr. Bohr-Gasse 7, A-1030 Vienna, Austria. The developmental potential of hematopoietic progenitors is restricted early on to either the erythromyeloid or lymphoid lineages. The broad developmental potential of Pax5(-/-) pro-B cells is in apparent conflict with such a strict separation, although these progenitors realize the myeloid and erythroid potential with lower efficiency compared to the lymphoid cell fates. Here we demonstrate that ectopic expression of the transcription factors C/EBPalpha, GATA1, GATA2 and GATA3 strongly promoted in vitro macrophage differentiation and myeloid colony formation of Pax5(-/-) pro-B cells. GATA2 and GATA3 expression also resulted in efficient engraftment and myeloid development of Pax5(-/-) pro-B cells in vivo. The myeloid transdifferentiation of Pax5(-/-) pro-B cells was accompanied by the rapid activation of myeloid genes and concomitant repression of B-lymphoid genes by C/EBPalpha and GATA factors. These data identify the Pax5(-/-) pro-B cells as lymphoid progenitors with a latent myeloid potential that can be efficiently activated by myeloid transcription factors. The same regulators were unable to induce a myeloid lineage switch in Pax5(+/+) pro-B cells, indicating that Pax5 dominates over myeloid transcription factors in B-lymphocytes. PMID: 12881423 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 21: Br J Haematol. 2002 Nov;119(2):510-5. Developmental changes in the expression of transcription factors GATA-1, -2 and -3 during the onset of human medullary haematopoiesis. Dame C, Sola MC, Fandrey J, Rimsza LM, Freitag P, Knopfle G, Christensen RD, Bungert J. Department of Pediatrics, University of Florida, Gainesville 32610-0296, USA. damec@peds.ufl.edu Regulation of gene expression during the ontogeny of haematopoiesis in the human fetal bone marrow is poorly understood. Studies in mice demonstrated that GATA-1, -2 and -3 play pivotal roles in haematopoiesis. In this study, we identified GATA-1-, GATA-2- and GATA-3-expressing cells in bone marrow sections and analysed the expression of GATA-transcription factors during the development of human fetal bone marrow haematopoiesis using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). We showed that GATA-1, -2 and -3 were expressed only in haematopoietic cells in the bone marrow. RT-PCR analysis demonstrated that (1) GATA-1 expression significantly increased during gestation; (2) GATA-2 expression peaked at the onset of medullary haematopoiesis, declined thereafter, and remained at a constant level after 30 weeks post conception; and (3) GATA-3 expression revealed no changes during development. The results indicated that the onset of medullary haematopoiesis in humans is accompanied by high expression of GATA-2, reflecting high proliferation rates of early haematopoietic progenitor cells, whereas expression of GATA-1 mirrors haematopoietic activity. PMID: 12406094 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 22: Dev Biol. 2002 Sep 1;249(1):30-43. GATA proteins identify a novel ventral interneuron subclass in the developing chick spinal cord. Karunaratne A, Hargrave M, Poh A, Yamada T. Department of Biochemistry, The University of Queensland, Brisbane, Queensland, 4072, Australia. a.karunaratne@salk.edu Members of the GATA transcription factor gene family have been implicated in a variety of developmental processes, including that of the vertebrate central nervous system. However, the role of GATA proteins in spinal cord development remains unresolved. In this study, we investigated the expression and function of two GATA proteins, GATA2 and GATA3, in the developing chick spinal cord. We show that both proteins are expressed by a distinct subpopulation of ventral interneurons that share the same dorsoventral position as CHX10-positive V2 interneurons. However, no coexpression is observed between the two GATA proteins and CHX10. By in vivo notochord grafting and cyclopamine treatment, we demonstrate that the spatially restricted pattern of GATA3 expression is regulated, at least in part, by the signaling molecule Sonic hedgehog. In addition, we further show that Sonic hedgehog induces GATA3 expression in a dose-dependent manner. Using in ovo electroporations, we also demonstrate that GATA2 is upstream of GATA3 in the same epigenetic cascade and that GATA3 is capable of inducing GATA2 expression in vivo. Furthermore, the ectopically expressed GATA proteins can repress differentiation of other ventral cell fates, but not the development of progenitor populations identified by PAX protein expression. Taken together, our findings strongly suggest an important role for GATA2 and GATA3 proteins in the establishment of a distinct ventral interneuron subpopulation in the developing chick spinal cord. PMID: 12217316 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 23: Exp Hematol. 2002 Aug;30(8):887-95. GATA transcription in a small rhodamine 123(low)CD34(+) subpopulation of a peripheral blood-derived CD34(-)CD105(+) mesenchymal cell line. Conrad C, Gottgens B, Kinston S, Ellwart J, Huss R. Institute of Pathology, University of Munich, Germany. OBJECTIVE: Based on previous animal experiments that suggest the plasticity of peripheral blood-derived, CD34(-) stem cell lines, the aim of this study was to isolate CD34(-) stem cell lines from human peripheral blood cells and obtain evidence of their multipotency and plasticity. MATERIALS AND METHODS: Adherent growing cells were isolated from peripheral blood mononuclear cells from a healthy volunteer donor and different cell clones were established after SV40 large-T-antigen-mediated immortalization. The immunophenotype of the cell lines was investigated by flow cytometry. One particular cell clone, V54/2, was stained with rhodamine 123, and the Rh123(low) and Rh123(high) subpopulations were sorted for a reverse transcriptase polymerase chain reaction gene expression survey and distinct differences in morphology and biologic behavior. RESULTS: The peripheral blood-derived and fibroblast-like cell line V54/2 expressed high levels of CD10 and CD105 and showed only a very low level expression of CD34 (<1.0%) and CD117 (c-kit). Among the entire CD34(-)CD105(+) cell population that transcribed factors such as Myb, Tie-1, and VEGF, there was a small Rh123(low)CD34(+) subpopulation that transcribed significant levels of several members of the GATA family of transcription factors. The morphology of the Rh123(low)CD34(+) (also expressing the P-glycoprotein) was different compared to the Rh123(high)CD34(-) population. Mesenchymal differentiation into glial fibrillary acidic protein (GFAP)(+) glial cells could be shown from the entire CD34(-)CD105(+) cell population. CONCLUSIONS: The findings provide evidence that it is possible to isolate CD34(-)CD105(+) mesenchymal stem cell lines from human peripheral blood cells that contain a small subpopulation of CD34(+) and GATA-transcribing cells. Those cells are potential hematopoietic progenitors and can be recruited from the CD34(-) stem cell pool. The plasticity of stem cells seems to require essential molecular tools, such as a panel of transcription factors, to respond to the environmental demand within a biologic system. PMID: 12160840 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 24: Plant Mol Biol. 2002 Sep;50(1):43-57. Arabidopsis thaliana GATA factors: organisation, expression and DNA-binding characteristics. Teakle GR, Manfield IW, Graham JF, Gilmartin PM. Centre for Plant Sciences, University of Leeds, UK. Many light-responsive promoters contain GATA motifs and a number of nuclear proteins have been defined that interact with these elements. Type-IV zinc-finger proteins have been extensively characterised in animals and fungi and are referred to as GATA factors by virtue of their affinity for promoter elements containing this sequence. We previously identified cDNA sequences representing four Arabidopsis thaliana type-TV zinc-finger proteins. Here we define the organisation and expression of GATA-1, GATA-2, GATA-3 and GATA-4 as well as DNA-binding characteristics of their encoded proteins. Transcripts from all four genes can be detected in all tissues examined suggesting that they are not developmentally regulated at the level of transcription. In vitro binding experiments with Escherichia coli-derived recombinant proteins were performed using motifs previously defined as targets for nuclear GATA-binding proteins. These studies reveal differences in DNA binding specificity of GATA-1 as compared to the other three proteins. In vivo protein-DNA interactions monitored by yeast one-hybrid assays reveal different binding characteristics as compared to those defined with E. coli-derived recombinant protein. Trans-activation of gene expression by the four Arabidopsis proteins via some, but not all, DNA elements tested indicates that the Arabidopsis proteins can form functional interactions with previously defined promoter elements containing GATA motifs. We conclude that the Arabidopsis type-IV zinc-finger proteins may represent the previously defined family of nuclear GATA-binding proteins implicated in light-responsive transcription. PMID: 12139008 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 25: Int J Hematol. 2002 May;75(4):376-81. GATA suppresses erythropoietin gene expression through GATA site in mouse erythropoietin gene promoter. Imagawa S, Suzuki N, Ohmine K, Obara N, Mukai HY, Ozawa K, Yamamoto M, Nagasawa T. Division of Hematology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan. simagawa@md.tsukuba.ac.jp The promoter and enhancer elements of the mouse erythropoietin (mEpo) gene, which have high homology with those of the human erythropoietin (hEpo) gene, were fused with luciferase. The construct was transfected into erythropoietin-producing hepatoma cell line (Hep3B) cells by lipofectin with lacZ as an internal standard. The wild type (TGATA) showed a 39.5-fold increase in induction by hypoxia. Mouse GATA-2 inhibited the hypoxic induction of the wild-type (m3), promoterluciferase construct but not the hypoxic induction of the mutant (m4, 5) promoter-luciferase constructs. N(G)-monomethyl L-arginine (L-NMMA) inhibited the hypoxic induction of the m3 promoter-luciferase construct, but this inhibition was recovered by L-arginine. H2O2 also inhibited the hypoxic induction of the m3 promoter-luciferase construct, but this inhibition was recovered by catalase. Gel shift assays performed on nuclear extracts of 293 cells overexpressing mGATA-1, -2, and -3 revealed that mGATA-1, -2, and -3 bind to the TGATA element of the mEpo promoter. These results indicate that mGATA binds to the TGATA site of the mEpo promoter and negatively regulates mEpo gene expression. Negative regulation of mEpo gene by GATA transcriptional factors is discussed. PMID: 12041667 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 26: Dev Biol. 2001 Oct 1;238(1):64-78. Hemangioblast commitment in the avian allantois: cellular and molecular aspects. Caprioli A, Minko K, Drevon C, Eichmann A, Dieterlen-Lievre F, Jaffredo T. Institut d'Embryologie Cellulaire et Moleculaire du CNRS et du College de France, 49 bis av. de la Belle Gabrielle, Nogent s/Marne Cedex, 94736, France. We recently identified the allantois as a site producing hemopoietic and endothelial cells capable of colonizing the bone marrow of an engrafted host. Here, we report a detailed investigation of some early cytological and molecular processes occurring in the allantoic bud, which are probably involved in the production of angioblasts and hemopoietic cells. We show that the allantois undergoes a program characterized by the prominent expression of several "hemangioblastic" genes in the mesoderm accompanied by other gene patterns in the associated endoderm. VEGF-R2, at least from stage HH17 onward, is expressed and is shortly followed by transcription factors GATA-2, SCL/tal-1, and GATA-1. Blood island-like structures differentiate that contain both CD45(+) cells and cells accumulating hemoglobin; these structures look exactly like blood islands in the yolk sac. This hemopoietic process takes place before the establishment of a vascular network connecting the allantois to the embryo. As far as the endoderm is concerned, GATA-3 mRNA is found in the region where allantois will differentiate before the posterior instestinal portal becomes anatomically distinct. Shortly before the bud grows out, GATA-2 was expressed in the endoderm and, at the same time, the hemangioblastic program became initiated in the mesoderm. GATA-3 is detected at least until E8 and GATA-2 until E3 the latest stage examined for this factor. Using in vitro cultures, we show that allantoic buds, dissected out before the establishment of circulation between the bud and the rest of the embryo, produced erythrocytes of the definitive lineage. Moreover, using heterospecific grafts between chick and quail embryos, we demonstrate that the allantoic vascular network develops from intrinsic progenitors. Taken together, these results extend our earlier findings about the commitment of mesoderm to the endothelial and hemopoietic lineages in the allantois. The detection of a prominent GATA-3 expression restricted to the endoderm of the preallantoic region and allantoic bud, followed by that of GATA-2, is an interesting and novel information, in the context of organ formation and endoderm specification in the emergence of hemopoietic cells. Copyright 2001 Academic Press. PMID: 11783994 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 27: Adv Exp Med Biol. 2001;495:15-24. Molecular characterization of gut T cell precursors in euthymic and athymic mice. Lambolez F, Rocha B. INSERM U.345, Institut Necker, 156 rue de Vaugirard, 75730 Paris, France. PMID: 11774559 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 28: J Biol Chem. 2002 Feb 1;277(5):3585-92. Epub 2001 Nov 27. Defects of the heart, eye, and megakaryocytes in peroxisome proliferator activator receptor-binding protein (PBP) null embryos implicate GATA family of transcription factors. Crawford SE, Qi C, Misra P, Stellmach V, Rao MS, Engel JD, Zhu Y, Reddy JK. Department of Pathology, Northwestern University School of Medicine, Chicago, Illinois 60611-3008, USA. Peroxisome proliferator activator receptor (PPAR)-binding protein (PBP) is an important coactivator for PPARgamma and other nuclear receptors. It has been identified as an integral component of a multiprotein thyroid hormone receptor-associated protein/vitamin D(3) receptor-interacting protein/activator-recruited cofactor complexes required for transcriptional activity. Here, we show that PBP is critical for the development of placenta and for the normal embryonic development of the heart, eye, vascular, and hematopoietic systems. The primary functional cause of embryonic lethality at embryonic day11.5 observed with PBP null mutation was cardiac failure because of noncompaction of the ventricular myocardium and resultant ventricular dilatation. There was a paucity of retinal pigment, defective lens formation, excessive systemic angiogenesis, a deficiency in the number of megakaryocytes, and an arrest in erythrocytic differentiation. Some of these defects involve PPARgamma and retinoid-sensitive sites, whereas others have not been recognized in the PPAR-signaling pathway. Phenotypic changes in four organ systems observed in PBP null mice overlapped with those in mice deficient in members of GATA, a family of transcription factors known to regulate differentiation of megakaryocytes, erythrocytes, and adipocytes. We demonstrate that PBP interacts with all five GATA factors analyzed, GATA-1, GATA-2, GATA-3, GATA-4, and GATA-6, and show that the binding of GATA-1, GATA-4, and GATA-6 to PBP is not dependent on the nuclear receptor recognition sequence motif LXXLL (where L is leucine and X is any amino acid) in PBP. Coexpression of PBP with GATA-3 markedly enhanced transcriptional activity of GATA-3 in nonhematopoietic cells. These observations identify the GATA family of transcription factors as a new interacting partner of PBP and demonstrate that PBP is essential for normal development of vital organ systems. PMID: 11724781 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 29: Biochem Biophys Res Commun. 2000 Nov 11;278(1):134-9. Genomic organization, chromosomal localization, and the complete 22 kb DNA sequence of the human GCMa/GCM1, a placenta-specific transcription factor gene. Yamada K, Ogawa H, Tamiya G, Ikeno M, Morita M, Asakawa S, Shimizu N, Okazaki T. Institute for Comprehensive Medical Science, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan. kyamada@fujita-hu.ac.jp The genomic sequence of the human GCMa/GCM1 gene, a mammalian homologue of Drosophila melanogaster GCM, was determined. Drosophila GCM is a neural transcription factor that regulates glial cell fate. The mammalian homolog however, is a placenta-specific transcription factor that is necessary for placental development. The 22 kb DNA sequence spanning the GCMa gene contains six exons and five introns, encoding a 2.8 kb cDNA. Overall genomic organization is similar for the human and mouse. Several potential binding sites for transcription factors like GATA, Oct-1, and bHLH proteins were found in the 5'-flanking region of the human gene. A DNA motif for GCM protein binding exists in the 5'-flanking region that is highly homologous with that of the mouse gene. The location of this gene was mapped to chromosome 6 using fluorescence in situ hybridization. Copyright 2000 Academic Press. PMID: 11071865 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 30: Science. 2000 Oct 6;290(5489):134-8. Function of GATA transcription factors in preadipocyte-adipocyte transition. Tong Q, Dalgin G, Xu H, Ting CN, Leiden JM, Hotamisligil GS. Division of Biological Sciences and Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA. Genes that control the early stages of adipogenesis remain largely unknown. Here, we show that murine GATA-2 and GATA-3 are specifically expressed in white adipocyte precursors and that their down-regulation sets the stage for terminal differentiation. Constitutive GATA-2 and GATA-3 expression suppressed adipocyte differentiation and trapped cells at the preadipocyte stage. This effect is mediated, at least in part, through the direct suppression of peroxisome proliferator-activated receptor gamma. GATA-3-deficient embryonic stem cells exhibit an enhanced capacity to differentiate into adipocytes, and defective GATA-2 and GATA-3 expression is associated with obesity. Thus, GATA-2 and GATA-3 regulate adipocyte differentiation through molecular control of the preadipocyte-adipocyte transition. PMID: 11021798 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 31: Mol Cell Endocrinol. 2000 Sep 25;167(1-2):43-53. A role for GATA transcription factors in the androgen regulation of the prostate-specific antigen gene enhancer. Perez-Stable CM, Pozas A, Roos BA. Geriatric Research, Education, and Clinical Center and Research Service, Veterans Affairs Medical Center, Miami, FL 33125, USA. cpsma@msn.com The transgenic mouse line Ggamma/T-15 containing the fetal globin promoter linked to SV40 T antigen unexpectedly results in androgen-independent prostate carcinomas. Given the key role of GATA-1 transcription factor in fetal globin gene promoter activity, we investigated whether specific GATA family members are expressed in the prostate and whether they can regulate prostate-specific genes. We found that GATA-2 and -3 are the predominant GATA family members expressed in human and mouse prostate and that GATA mRNA levels are not regulated by androgen. We identified six GATA sites flanking an androgen-response element located in the far-upstream enhancer of the prostate-specific antigen (PSA) gene. These GATA sites are targets for GATA factors and are essential for optimal androgen induction of transfected PSA enhancer/promoter plasmids in LNCaP, a PSA and androgen receptor expressing human prostate cancer cell line. Our results suggest that prostatic GATA-2 and -3 are involved in the androgen regulation of the PSA gene. PMID: 11000519 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 32: Blood. 2000 Aug 1;96(3):910-6. GATA factor transgenes under GATA-1 locus control rescue germline GATA-1 mutant deficiencies. Takahashi S, Shimizu R, Suwabe N, Kuroha T, Yoh K, Ohta J, Nishimura S, Lim KC, Engel JD, Yamamoto M. Institute of Basic Medical Sciences and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Japan. GATA-1 germline mutation in mice results in embryonic lethality due to defective erythroid cell maturation, and thus other hematopoietic GATA factors do not compensate for the loss of GATA-1. To determine whether the obligate presence of GATA-1 in erythroid cells is due to its distinct biochemical properties or spatiotemporal patterning, we attempted to rescue GATA-1 mutant mice with hematopoietic GATA factor complementary DNAs (cDNAs) placed under the transcriptional control of the GATA-1 gene. We found that transgenic expression of a GATA-1 cDNA fully abrogated the GATA-1-deficient phenotype. Surprisingly, GATA-2 and GATA-3 factors expressed from the same regulatory cassette also rescued the embryonic lethal phenotype of the GATA-1 mutation. However, adult mice rescued with the latter transgenes developed anemia, while GATA-1 transgenic mice did not. These results demonstrate that the transcriptional control dictating proper GATA-1 accumulation is the most critical determinant of GATA-1 activity during erythropoiesis. The results also show that there are biochemical distinctions among the hematopoietic GATA proteins and that during adult hematopoiesis the hematopoietic GATA factors are not functionally equivalent. PMID: 10910904 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 33: Development. 1999 Dec;126(23):5523-31. The transcription factor GATA3 is a downstream effector of Hoxb1 specification in rhombomere 4. Pata I, Studer M, van Doorninck JH, Briscoe J, Kuuse S, Engel JD, Grosveld F, Karis A. Institute of Molecular and Cell Biology, University of Tartu, 51010 Tartu, Estonia. In this paper, we show that the transcription factor GATA3 is dynamically expressed during hindbrain development. Function of GATA3 in ventral rhombomere (r) 4 is dependent on functional GATA2, which in turn is under the control of Hoxb1. In particular, the absence of Hoxb1 results in the loss of GATA2 expression in r4 and the absence of GATA2 results in the loss of GATA3 expression. The lack of GATA3 expression in r4 inhibits the projection of contralateral vestibuloacoustic efferent neurons and the migration of facial branchiomotor neurons similar to Hoxb1-deficient mice. Ubiquitous expression of Hoxb1 in the hindbrain induces ectopic expression of GATA2 and GATA3 in ventral r2 and r3. These findings demonstrate that GATA2 and GATA3 lie downstream of Hoxb1 and provide the first example of Hox pathway transcription factors within a defined population of vertebrate motor neurons. PMID: 10556076 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 34: Mech Dev. 1999 Sep;87(1-2):213-6. Gata2 and Gata3: novel markers for early embryonic polarity and for non-neural ectoderm in the chick embryo. Sheng G, Stern CD. Department of Genetics and Development, Columbia University, 701 West 168th Street #1602, New York, New York 10032, USA. We have investigated in detail the expression patterns of two Gata genes, cGata2 and cGata3, during early chick development. In addition to confirming previously described expression of these two genes in developing brain, kidney and blood islands, this study reveals several important novel expression domains during very early stages of development. cGata2 is expressed in the area opaca in pre-primitive streak stages, forming a gradient along the A-P axis (strongest anteriorly). Both genes are expressed strongly in the entire non-neural ectoderm from stage 4+, and neither is expressed in prospective neural plate at any stage. Unlike other previously described non-neural markers, neither gene is expressed in the dorsal neural tube. We also describe dynamic expression of cGata2 and cGata3 during eye, ear and gut development. PMID: 10495290 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 35: Dev Biol. 1999 Jun 15;210(2):305-21. Expression and genetic interaction of transcription factors GATA-2 and GATA-3 during development of the mouse central nervous system. Nardelli J, Thiesson D, Fujiwara Y, Tsai FY, Orkin SH. Cytosquelette et Developpement, CNRS URA 2115, CHU Pitie-Salpetriere, 105 Boulevard de l'Hopital, Paris Cedex, 75 634, France. nardelli@idf.ext.jussieu.fr Here we examine the expression of transcription factors GATA-2 and GATA-3 during early stages of embryonic development in the central nervous system (CNS) of the mouse. GATA-2 is expressed as early as 9 dpc in the hindbrain, in ventral rhombomere 4, and transiently in ventral rhombomere 2 (r2). From 9.5 to 11.5 dpc, activation of the gene spreads to many sites of early neuronal differentiation, such as the olfactory bulbs, the pretectum, and the oculomotor nucleus in the midbrain, a thin stripe of cells lining the floor plate from the mesencephalon to the cervical spinal cord and a ventral column of cells spanning the neural tube from rostral hindbrain and including motor neuron as well as ventral interneuron precursors. GATA-3 is expressed in a pattern very similar to that of GATA-2. Distinguishing features are the lack of expression in r2 at 9 dpc and a slight delay in its activation. In addition, GATA-2 is activated in both the ventricular and the subventricular zones of the neural tube, whereas GATA-3 is restricted mainly to the subventricular zone. Expression analyses performed on GATA-2 -/- mouse embryos between E9.5 and 10.5 dpc established that: (i) the expression of GATA-3 in the developing CNS of the mouse embryo is dependent on the presence of GATA-2 and (ii) loss of GATA-2 leads to severe defects in neurogenesis, which strongly suggests that GATA-2 is involved, as in hematopoiesis, in the maintenance of the pool of ventral neuronal progenitors. Copyright 1999 Academic Press. PMID: 10357893 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 36: Int J Dev Biol. 1998 Sep;42(6):763-74. Evidence for non-axial A/P patterning in the nonneural ectoderm of Xenopus and zebrafish pregastrula embryos. Read EM, Rodaway AR, Neave B, Brandon N, Holder N, Patient RK, Walmsley ME. Developmental Biology Research Centre, King's College London, The Randall Institute, United Kingdom. Recent studies in early Xenopus and zebrafish embryos have demonstrated that posteriorizing, non-axial signals arising from outside the organizer (or shield) contribute to A/P patterning of the neural axis, in contradiction to the classical Spemann model in which such signals were proposed to be solely organizer derived. Our studies on the early expression of the transcription factors GATA-2 and 3 in both Xenopus and zebrafish nonneural ectoderm lend support to the existence of such non-axial signaling in the A/P axis. Thus we find that the earliest expression of GATA-2 and 3 is located in nonneural ectoderm and is strongly patterned in a graded manner along the A/P axis, being high anteriorly and absent from the most posterior regions. This results by early neurula stages in three broad zones: an anterior region which is positive for both GATA-2 and 3, a middle region which is positive for GATA-2 alone and a posterior region in which neither gene is expressed. These regions correspond to head, trunk and tail ectoderm and may represent the beginnings of functional segmentation of nonneural ectoderm, as suggested in the concept of the 'ectomere'. We find that A/P patterning of GATA expression in nonneural ectoderm may occur as early as late blastula/early gastrula stages. We investigate which posteriorizing signals might contribute to such distinct non axial ectodermal patterning in the A/P axis and provide evidence that both FGF and a Wnt family member contribute towards the final A/P pattern of GATA expression in nonneural ectoderm. PMID: 9727832 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 37: J Virol. 1998 Jul;72(7):5579-88. Members of the GATA family of transcription factors bind to the U3 region of Cas-Br-E and graffi retroviruses and transactivate their expression. Barat C, Rassart E. Laboratoire de Biologie Moleculaire, Departement de Sciences Biologiques, Universite du Quebec a Montreal, Montreal, Quebec, Canada H3C 3P8. Cas-Br-E and Graffi are two murine viruses that induce myeloid leukemia in mice: while Cas-Br-E induces mostly non-T, non-B leukemia composed of very immature cells, Graffi causes exclusively a granulocytic leukemia (E. Rassart, J. Houde, C. Denicourt, M. Ru, C. Barat, E. Edouard, L. Poliquin, and D. Bergeron, Curr. Top. Microbiol. Immunol. 211:201-210, 1995). In an attempt to understand the basis of the myeloid specificity of these two retroviruses, we used DNase I footprinting analysis and gel mobility shift assays to identify a number of protein binding sites within the Cas-Br-E and Graffi U3 regions. Two protected regions include potential GATA binding sites. Methylation interference analysis with different hematopoietic nuclear extracts showed the importance of the G residues in these GATA sites, and supershift assays clearly identified the binding factors as GATA-1, GATA-2, and GATA-3. Transient assays with long terminal repeat (LTR)-chloramphenicol acetyltransferase constructs showed that these three GATA family members are indeed able to transactivate Cas-Br-E and Graffi LTRs. Thus, the availability and relative abundance of the various members of the GATA family of transcription factors in a given cell type could influence the transcriptional tissue specificity of murine leukemia viruses and hence their disease specificity. PMID: 9621016 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 38: Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1641-6. Blood-borne seeding by hematopoietic and endothelial precursors from the allantois. Caprioli A, Jaffredo T, Gautier R, Dubourg C, Dieterlen-Lievre F. Institut d'Embryologie cellulaire et moleculaire du Centre National de la Recherche Scientifique et du College de France 49bis, av. de la Belle Gabrielle, 94736 Nogent s/Marne cedex, France. caprioli@infobiogen.fr Until now the allantois has not been considered as a hematopoietic organ. Here we report experimental evidence demonstrating the in situ emergence of both hematopoietic and endothelial precursors in the avian allantoic bud. When the prevascularized allantoic bud from a quail embryo was grafted in the coelom of a chicken host, hematopoietic and endothelial cells later were found in the bone marrow of the host. Because the graft was located at a distance from the limb bud, these cells could reach the bone marrow only by the circulatory pathway. This blood-borne seeding may be accomplished by distinct hematopoietic and endothelial precursors, or by hemangioblasts, the postulated common precursors of these two lineages; we consider the latter interpretation more likely. We also show by reverse transcription-PCR that the allantois region expresses very early the GATA genes involved in hematopoiesis and some beta-globin chain genes. PMID: 9465069 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 39: Endocrinology. 1997 Aug;138(8):3417-25. The proximal promoter region of the gene encoding human 17beta-hydroxysteroid dehydrogenase type 1 contains GATA, AP-2, and Sp1 response elements: analysis of promoter function in choriocarcinoma cells. Piao YS, Peltoketo H, Vihko P, Vihko R. Biocenter Oulu and Department of Clinical Chemistry, University of Oulu, Finland. The 5'-flanking region from -78 to +9 in the HSD17B1 gene serves as a promoter, and an HSD17B1 silencer element is located in position -113 to -78. In the present studies, we have characterized three regulatory elements in the proximal 5'-flanking regions of the gene, using electrophoretic mobility shift assays and reporter gene analysis. First, nuclear factors recognized by antibodies against Sp1 and Sp3 were found to bind the Sp1 motif in the region from -52 to -43. Mutation of the Sp1-binding site decreased the promoter activity to 30% in JEG-3 cells and to 60% in JAR cells, suggesting that binding to the Sp1 motif has a substantial role in the complete functioning of the HSD17B1 promoter. Second, the binding of AP-2 to its motif in the region from -62 to -53 led to reduced binding of Sp1 and Sp3, and furthermore, mutation of the AP-2 element increased promoter activity to 260% in JEG-3 cells. The data thus implied that AP-2 can repress the function of the HSD17B1 promoter by preventing binding to the Sp1 motif. Finally, GATA factors, GATA-3 in particular, were demonstrated to bind their cognate sequence in the HSD17B1 silencer region, and mutations introduced into the GATA-binding site increased transcriptional activity to the level seen in constructs not containing the silencer element. Thus, GATA-3 seems to prevent transcription in the constructs, and hence, the GATA motif also may operate as a negative control element for HSD17B1 transcription. PMID: 9231796 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 40: EMBO J. 1997 May 15;16(10):2874-82. The N-terminal fingers of chicken GATA-2 and GATA-3 are independent sequence-specific DNA binding domains. Pedone PV, Omichinski JG, Nony P, Trainor C, Gronenborn AM, Clore GM, Felsenfeld G. Laboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892-0520, USA. The GATA family of vertebrate DNA binding regulatory proteins are expressed in diverse tissues and at different times of development. However, the DNA binding regions of these proteins possess considerable homology and recognize a rather similar range of DNA sequence motifs. DNA binding is mediated through two domains, each containing a zinc finger. Previous results have led to the conclusion that although in some cases the N-terminal finger can contribute to specificity and strength of binding, it does not bind independently, whereas the C-terminal finger is both necessary and sufficient for binding. Here we show that although this is true for the N-terminal finger of GATA-1, those of GATA-2 and GATA-3 are capable of strong independent binding with a preference for the motif GATC. Binding requires the presence of two basic regions located on either side of the N-terminal finger. The absence of one of these near the GATA-1 N-terminal finger probably accounts for its inability to bind. The combination of a single finger and two basic regions is a new variant of a motif that has been previously found in the binding domains of other finger proteins. Our results suggest that the DNA binding properties of the N-terminal finger may help distinguish GATA-2 and GATA-3 from GATA-1 and the other GATA family members in their selective regulatory roles in vivo. PMID: 9184231 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 41: Leukemia. 1997 Apr;11 Suppl 3:501-2. Of the GATA-binding proteins, only GATA-4 selectively regulates the human IL-5 gene promoter in IL-5 producing cells which express multiple GATA-binding proteins. Yamagata T, Nishida J, Sakai R, Tanaka T, Yazaki Y, Hirai H. Interleukin-5 (IL-5) is produced by T lymphocytes and known to support B cell growth and eosinophilic differentiation of the progenitor cells. Using ATL-16T cells which express IL-5 mRNA, we have identified a region, within the human IL-5 gene promoter, that regulates IL-5 gene transcription. This cis-acting sequence contains the core binding motif, (A/T)GATA(A/G), for GATA-binding family proteins and thus suggests the involvement of these family members. In this report, we describe the cloning of human GATA-4 (hGATA-4) and show that hGATA-4 selectively interacts with the -70 GATA site within the IL-5 proximal promoter region. By promoter deletion and mutation analyses, we established this region as a positive regulatory element. Cotransfection experiments revealed that both hGATA-4 and PMA/A23187 stimulation are necessary for the IL-5 promoter activation. The requirement of another regulatory element called CLE0, which lies downstream of the -70 GATA site, was also demonstrated. ATL-16T cells express mRNA of three GATA-binding proteins, hGATA-2, hGATA-3 and hGATA-4, and each of them has a potential to bind to the consensus (A/T)GATA(G/ A) motif. However, using ATL-16T nuclear extract, we demonstrated that GATA-4 is the only GATA-binding protein that forms specific DNA-protein complex with the -70 GATA site. The electrophoretic mobility shift assay with extracts of COS cells expressing GATA-binding proteins showed that GATA-4 has the highest binding affinity to the -70 GATA site among the three GATA-binding proteins. When the transactivation ability was compared among the three, GATA-4 showed the highest activity. These results demonstrate the selective role of GATA-4 in the transcriptional regulation of the IL-5 gene in a circumstance where multiple members of the GATA-binding proteins are expressed. PMID: 9209438 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 42: Int J Hematol. 1997 Apr;65(3):239-49. Expression of GATA transcription factors in myelogenous and lymphoblastic leukemia cells. Minegishi N, Morita S, Minegishi M, Tsuchiya S, Konno T, Hayashi N, Yamamoto M. Department of Biochemistry, School of Medicine, Tohoku University, Sendai, Japan. In the hematopoietic lineage, the transcription factors GATA-1 and GATA-2 show restricted and largely overlapping expression profiles, but GATA-2 is uniquely expressed in early hematopoietic progenitors. GATA-3 is found exclusively in T cells of hematopoietic lineage. To clarify whether these expression profiles are preserved or changed during the development of malignancies, we analyzed the expression of GATA factors in the blasts from leukemic children. A total of 18 myelogenous leukemia and 24 lymphoblastic leukemia (ALL) cases were investigated. In the majority of the former cases, GATA-2 mRNA expression and the expression of CD34 and c-kit antigens on leukemic cells were demonstrated. In contrast, GATA-2 mRNA and c-kit antigen could not be detected in CD34-positive cells from ALL patients. GATA-3 mRNA was expressed in all T-ALL cases, but not in any precursor B-ALL. These findings suggest that down-regulation of GATA-2 and expression of GATA-3 are important events for the commitment of cells to lymphoid and T cell lineage, respectively. The expression profiles of GATA factors in leukemic cells are generally consistent with those in their normal counterparts, and thus provide a useful tool to determine the lineage commitment of unclassified leukemia. PMID: 9114595 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 43: Biochem Biophys Res Commun. 1997 Mar 6;232(1):65-8. Regulation of aquaporin-2 gene transcription by GATA-3. off. Uchida S, Matsumura Y, Rai T, Sasaki S, Marumo F. Second Department of Internal Medicine, School of Medicine, Tokyo Medical and Dental University, Japan. suchida.med2@med.tmd.ac.jp To evaluate the functional role of GATA motifs in the 5'-flanking region of a kidney-specific AQP-2 water channel gene, we sought to isolate a GATA factor(s) expressed in collecting ducts and determined the role on the AQP-2 promoter. Two cDNAs encoding GATA factors were isolated from rat kidney, whose sequences were highly homologous with human GATA-2 and -3. Reverse-transcription PCR using dissected nephron segments revealed that rat GATA-3 but not GATA-2 was expressed in collecting ducts, thus indicating that GATA-3 could interact with GATA motifs in the AQP-2 promoter. Transactivation experiments utilizing the rat GATA-3 expression vector indicated that rat GATA-3 increased the AQP-2 promoter activity about fourfold. These results indicated that GATA motifs in the 5'-flanking region of the hAQP-2 gene were functional cis-elements and that GATA-3 in collecting ducts may be one of the important regulators of AQP-2 expression in vivo. PMID: 9125153 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 44: Blood. 1997 Feb 15;89(4):1430-9. Negative regulation of the erythropoietin gene expression by the GATA transcription factors. Imagawa S, Yamamoto M, Miura Y. Department of Medicine, Jichi Medical School, Tochigi-ken, Japan. We examined regulation of the human erythropoietin (Epo) gene through the GATA sequence in the Epo promoter and showed that Hep3B and HepG2 cells express human GATA-2 (hGATA-2) mRNA and protein. Nuclear extracts of QT6 cells transfected with hGATA-1, 2, or 3 transcription factors showed specific binding to the GATA element in the human Epo gene promoter by gel mobility shift assay. Transient transfection of Hep3B cells with hGATA-1, 2, or 3 showed that each of these transcription factors significantly decreased the level of expression of Epo mRNA as assessed by a competitive polymerase chain reaction. Transient transfection of Hep3B cells with hGATA-1, 2, and 3 and an Epo-reporter gene (growth hormone [GH]) construct showed significant inhibition of the Epo promoter. Antisense oligonucleotide for hGATA-2 transcription factor significantly increased the Epo protein in Hep3B cells under 1% O2 for 24 hours incubation. Furthermore, transient transfection of Hep3B cells with hGATA-1, 2, and 3 and an Epo-reporter gene (luciferase) construct also showed significant inhibition of the Epo promoter. However, transfection of the mutated GATA sequence of the Epo-luciferase gene with hGATA-1, 2, and 3 interfere with the inhibition of the Epo promoter. We conclude that the hGATA-1, 2, and 3 transcription factors specifically bind to the GATA element in the human Epo gene promoter and negatively regulate Epo gene expression. PMID: 9028967 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 45: Development. 1997 Feb;124(4):907-14. GATA-2 and GATA-3 regulate trophoblast-specific gene expression in vivo. Ma GT, Roth ME, Groskopf JC, Tsai FY, Orkin SH, Grosveld F, Engel JD, Linzer DI. Department of Biochemistry, Northwestern University, Evanston, Illinois 60208, USA. We previously demonstrated that the zinc finger transcription factors GATA-2 and GATA-3 are expressed in trophoblast giant cells and that they regulate transcription from the mouse placental lactogen I gene promoter in a transfected trophoblast cell line. We present evidence here that both of these factors regulate transcription of the placental lactogen I gene, as well as the related proliferin gene, in trophoblast giant cells in vivo. Placentas lacking GATA-3 accumulate placental lactogen I and proliferin mRNAs to a level 50% below that reached in the wild-type placenta. Mutation of the GATA-2 gene had a similar effect on placental lactogen I expression, but led to a markedly greater reduction (5- to 6-fold) in proliferin gene expression. Placentas lacking GATA-2 secrete significantly less angiogenic activity than wild-type placentas as measured in an endothelial cell migration assay, consistent with a reduction in expression of the angiogenic hormone proliferin. Furthermore, within the same uterus the decidual tissue adjacent to mutant placentas displays markedly reduced neovascularization compared to the decidual tissue next to wild-type placentas. These results indicate that GATA-2 and GATA-3 are important in vivo regulators of trophoblast-specific gene expression and placental function, and reveal a difference in the effect of these two factors in regulating the synthesis of related placental hormones. PMID: 9043071 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 46: C R Seances Soc Biol Fil. 1997;191(1):105-11. [Genetic control of hematopoiesis] [Article in French] Romeo PH. INSERM U91, Hopital Henri-Mondor, Creteil, France. Commitment and differentiation of hematopoietic stem cells are associated with the progressive restriction of cellular proliferation and the progressive expression of a subset of genes encoding the markers of mature cells. These two processes are genetically regulated and, in this paper, I review the expression and function of the GATA family of transcription factors as an example of this genetic regulation. GATA cis-acting elements are found in most of the regulatory regions of T-lymphoid, erythrocytic and megakaryocytic restricted genes. These GATA motifs are recognized by the members of a family of transcriptional regulators: the GATA family. Three members of this family, GATA-1, 2 and 3 are expressed in hematopoietic cells. They are necessary for the erythrocytic and megakaryocytic lineages (GATA-1), for the T-lymphoid lineage (GATA-3), and for the proliferation of uncommitted hematopoietic precursors (GATA-2). GATA-1 displays at least four functions: activation of the erythrocytic and megakaryocytic specific genes, regulation of the epsilon-->gamma globin switch and control of the cell cycle. These two last functions will be discussed to show the multiple facets of GATA-1 in the genetic regulation of hematopoiesis. Publication Types: Review Review, Tutorial PMID: 9181132 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 47: EMBO J. 1996 Jan 15;15(2):319-33. GATA transcription factors associate with a novel class of nuclear bodies in erythroblasts and megakaryocytes. Elefanty AG, Antoniou M, Custodio N, Carmo-Fonseca M, Grosveld FG. National Institute for Medical Research, UK. The nuclear distribution of GATA transcription factors in murine haemopoietic cells was examined by indirect immunofluorescence. Specific bright foci of GATA-1 fluorescence were observed in erythroleukaemia cells and primary murine erythroblasts and megakaryocytes, in addition to diffuse nucleoplasmic localization. These foci, which were preferentially found adjacent to nucleoli or at the nuclear periphery, did not represent sites of active transcription or binding of GATA-1 to consensus sites in the beta-globin loci. Immunoelectron microscopy demonstrated the presence of intensely labelled structures likely to represent the GATA-1 foci seen by immunofluorescence. The GATA-1 nuclear bodies differed from previously described nuclear structures and there was no co-localization with nuclear antigens involved in RNA processing or other ubiquitous (Spl, c-Jun and TBP) or haemopoietic (NF-E2) transcription factors. Interestingly, GATA-2 and GATA-3 proteins also localized to the same nuclear bodies in cell lines co-expressing GATA-1 and -2 or GATA-1 and -3 gene products. This pattern of distribution is, thus far, unique to the GATA transcription factors and suggests a protein-protein interaction with other components of the nuclear bodies via the GATA zinc finger domain. PMID: 8617207 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 48: Nat Genet. 1995 Sep;11(1):9-11. Comment on: Nat Genet. 1995 Sep;11(1):40-4. Gotta have GATA. Simon MC. Publication Types: Comment News PMID: 7550322 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 49: Nat Genet. 1995 Sep;11(1):40-4. Comment in: Nat Genet. 1995 Sep;11(1):9-11. Targeted disruption of the GATA3 gene causes severe abnormalities in the nervous system and in fetal liver haematopoiesis. Pandolfi PP, Roth ME, Karis A, Leonard MW, Dzierzak E, Grosveld FG, Engel JD, Lindenbaum MH. Dept. of Haematology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK. GATA-3 is one member of a growing family of related transcription factors which share a strongly conserved expression pattern in all vertebrate organisms. In order to elucidate GATA-3 function using a direct genetic approach, we have disrupted the murine gene by homologous recombination in embryonic stem cells. Mice heterozygous for the GATA3 mutation are fertile and appear in all respects to be normal, whereas homozygous mutant embryos die between days 11 and 12 postcoitum (p.c.) and display massive internal bleeding, marked growth retardation, severe deformities of the brain and spinal cord, and gross aberrations in fetal liver haematopoiesis. PMID: 7550312 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 50: Mol Cell Biol. 1995 Aug;15(8):4225-31. Cooperative interaction of GATA-2 and AP1 regulates transcription of the endothelin-1 gene. Kawana M, Lee ME, Quertermous EE, Quertermous T. Division of Cardiology, Vanderbilt University Medical School, Nashville, Tennessee 37232, USA. Endothelin-1 (ET-1) is a 21-amino-acid vasoactive peptide initially characterized as a product of endothelial cells. Reporter gene transfection experiments have indicated that a GATA site and an AP1 site are essential for ET-1 promoter function in endothelial cells, and GATA-2 appears to be the active GATA factor which regulates ET-1 expression. To look for interactions between AP1 and GATA-2, transactivation experiments were performed with expression vectors encoding c-Jun, c-Fos, and GATA-2. Cooperativity between the AP1 complex and GATA-2 was observed as a synergistic increase in transcriptional activity of the ET-1 reporter plasmid. In addition, AP1 was able to potentiate the action of GATA-2 on reporter constructs lacking a functional AP1 site. In a similar fashion, GATA-2 was able to potentiate the action of AP1 despite deletion of the GATA site. Experiments with GATA-1 and GATA-3 expression vectors provided evidence that this capacity to interact with AP1 may be a characteristic of all GATA family members. Biochemical evidence for AP1-GATA interaction was provided by immunoprecipitation experiments. A GATA-2-specific antiserum was shown to immunoprecipitate in vitro-synthesized Jun and Fos protein from reticulocyte lysate. Also, antisera directed against Jun and Fos were able to immunoprecipitate from nuclear extracts a GATA-binding protein, indicating the association of AP1 and GATA proteins in vivo. PMID: 7623817 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 51: Mol Cell Biol. 1995 Jul;15(7):3830-9. Of the GATA-binding proteins, only GATA-4 selectively regulates the human interleukin-5 gene promoter in interleukin-5-producing cells which express multiple GATA-binding proteins. Yamagata T, Nishida J, Sakai R, Tanaka T, Honda H, Hirano N, Mano H, Yazaki Y, Hirai H. Third Department of Internal Medicine, Tokyo University, Japan. Interleukin-5 (IL-5) is produced by T lymphocytes and known to support B-cell growth and eosinophilic differentiation of the progenitor cells. Using ATL-16T cells which express IL-5 mRNA, we have identified a region within the human IL-5 gene promoter that regulates IL-5 gene transcription. This cis-acting sequence contains the core binding motif, (A/T)GATA(A/G), for GATA-binding family proteins and thus suggests the involvement of this family members. In this report, we describe the cloning of human GATA-4 (hGATA-4) and show that hGATA-4 selectively interacts with the -70 GATA site within the IL-5 proximal promoter region. By promoter deletion and mutation analyses, we established this region as a positive regulatory element. Cotransfection experiments revealed that both hGATA-4 and phorbol-12-myristate-13-acetate (PMA)-A23187 stimulation are necessary for IL-5 promoter activation. The requirement for another regulatory element called CLE0, which lies downstream of the -70 GATA site, was also demonstrated. ATL-16T cells express mRNAs of three GATA-binding proteins, hGATA-2, hGATA-3, and hGATA-4, and each of them has a potential to bind to the consensus (A/T)GATA(G/A) motif. However, using ATL-16T nuclear extract, we demonstrated that GATA-4 is the only GATA-binding protein that forms a specific DNA-protein complex with the -70 GATA site. An electrophoretic mobility shift assay with extracts of COS cells expressing GATA-binding proteins showed that GATA-4 has the highest binding affinity for the -70 GATA site among the three GATA-binding proteins. When the transactivation abilities were compared among the three, GATA-4 showed the highest activity. These results demonstrate the selective role of GATA-4 in the transcriptional regulation of the IL-5 gene in a circumstance where multiple members of the GATA-binding proteins are expressed. PMID: 7791790 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 52: Oncogene. 1995 Feb 16;10(4):631-9. Regulation of lineage restricted haemopoietic transcription factors in cell hybrids. Murrell AM, Green AR. University of Cambridge, Department of Haematology, MRC Centre, UK. SCL, GATA-1, GATA-2 and GATA-3 encode lineage restricted haemopoietic transcription factors. We have previously shown that SCL, GATA-1 and GATA-2 are expressed in multipotent progenitors prior to lineage commitment, but are down-regulated during granulocyte/monocyte differentiation. The phenomenon of gene extinction in cell hybrids may reveal negative regulatory mechanisms operating during normal differentiation. We have therefore analysed the regulation of SCL, GATA-1, GATA-2 and GATA-3 in cell hybrids formed by the fusion of cell lines representing different haemopoietic lineages. Expression of GATA-3 was extinguished in both human and murine erythroid x T cell hybrids, an observation which suggests that erythroid cells contain factors capable of repressing GATA-3 expression. By contrast expression of SCL, GATA-1 and GATA-2 was not extinguished in erythroid x T or in erythroid x B cell hybrids. These data suggest that T cells and B cells do not contain trans-acting factors capable of down-regulating expression of SCL, GATA-1 or GATA-2, and therefore raise the possibility that a 'hit and run' mechanism may repress these genes during normal haemopoiesis. HpaII sites within the SCL promoter were unmethylated in erythroid cells but methylated in T cells. Erythroid x T and erythroid x B cell hybrids contained both methylated and unmethylated SCL promoters, thus implicating a heritable cis-acting mechanism in the regulation of the SCL gene in lymphoid cell lines. These results provide the first analysis of SCL and GATA gene regulation in stable cell hybrids. PMID: 7862440 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 53: Development. 1994 Nov;120(11):3257-66. GATA factor activity is required for the trophoblast-specific transcriptional regulation of the mouse placental lactogen I gene. Ng YK, George KM, Engel JD, Linzer DI. Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL 60208-3500. The molecular determinants governing tissue-specific gene expression in the placenta are at present only poorly defined, particularly with respect to the regulation of specific hormone genes whose products are vital to embryonic development and the maintenance of a nurturing maternal environment. In continuing our analysis of the trophoblast-specific expression of the mouse placental lactogen I gene, we now demonstrate that the transcription factors GATA-2 and GATA-3 regulate the activity of this gene promoter. These factors are expressed in placental trophoblast cells, with peak levels of the GATA-2, GATA-3 and placental lactogen I mRNAs each accumulating at midgestation. Analysis of a region of the placental lactogen I gene promoter, previously shown to be sufficient for directing trophoblast-specific transcription, revealed the presence of three consensus binding sites for GATA-2 or GATA-3. Both GATA-2 and GATA-3 bind to these sites in vitro and mutation of these sites results in a significant decrease in promoter activity as assayed by transient transfection into the choriocarcinoma-derived cell line Rcho-1, which expresses endogenous GATA-2 and GATA-3. Furthermore, overexpression of GATA factors in Rcho-1 cells stimulates transcription from a co-transfected placental lactogen I gene promoter. Most significantly, expression of GATA-2 or GATA-3 was found to induce transcription from this promoter in transfected non-trophoblast (fibroblast) cells. These data indicate that GATA factors are both limiting and required transcriptional regulatory molecules in placental trophoblasts, and that the tissue specificity of the placental lactogen I gene is determined, at least in part, by GATA-2 and/or GATA-3. PMID: 7720565 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 54: Seikagaku. 1994 Aug;66(8):1138-42. [Structure and function of GATA transcription factors; possible roles in cell differentiation] [Article in Japanese] Muraosa Y, Yamamoto M. Department of Biochemistry, Tohoku University School of Medicine, Sendai. Publication Types: Review Review, Tutorial PMID: 7963854 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 55: Mol Cell Biol. 1994 Aug;14(8):5592-602. GATA-binding proteins regulate the human gonadotropin alpha-subunit gene in the placenta and pituitary gland. Steger DJ, Hecht JH, Mellon PL. Department of Reproductive Medicine, University of California, San Diego, La Jolla 92093-0674. The human glycoprotein hormone alpha-subunit gene is expressed in two quite dissimilar tissues, the placenta and anterior pituitary. Tissue-specific expression is determined by combinations of elements, some of which are common and others of which are specific to each tissue. In the placenta, a composite enhancer confers specific expression. It contains four protein-binding sites: two cyclic AMP (cAMP) response elements that bind CREB, a trophoblast-specific element that binds TSEB, and a sequence motif, AGATAA, that matches the consensus binding site for a family of transcription factors termed the GATA-binding proteins. In pituitary gonadotropes, the cAMP response elements remain important for expression, TSEB is absent, and elements further upstream participate in tissue-specific expression. Here we establish a regulatory role for the GATA element in both the placenta and pituitary by demonstrating that a mutation of this element decreases alpha-subunit gene expression 15-fold in JEG-3 human placental cells and 2.5-fold in alpha T3-1 mouse pituitary gonadotropes. In JEG-3 cells, human GATA-2 (hGATA-2) and hGATA-3 are highly expressed and both proteins bind to the alpha-subunit gene GATA element. In alpha T3-1 cells, the GATA motif is bound by mouse GATA-2 (mGATA-2) and an mGATA-4-related protein. Cotransfection of hGATA-2 or hGATA-3 into alpha T3-1 cells activates the alpha-subunit gene threefold. These studies establish a role for the GATA-binding proteins in placental and pituitary alpha-subunit gene expression, significantly expanding the known target genes of GATA-2, GATA-3, and perhaps GATA-4. PMID: 7518566 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 56: Genes Dev. 1994 May 15;8(10):1184-97. Novel insights into erythroid development revealed through in vitro differentiation of GATA-1 embryonic stem cells. Weiss MJ, Keller G, Orkin SH. Division of Hematology-Oncology, Children's Hospital, Dana Farber Cancer Institute, Boston, Massachusetts. Mouse embryonic stem (ES) cells lacking the transcription factor GATA-1 do not produce mature red blood cells either in vivo or in vitro. To define the consequences of GATA-1 loss more precisely, we used an in vitro ES cell differentiation assay that permits enumeration of primitive (EryP) and definitive (EryD) erythroid precursors and recovery of pure erythroid colonies. In contrast to normal ES cells, GATA-1- ES cells fail to generate EryP precursors. EryD precursors, however, are normal in number but undergo developmental arrest and death at the proerythroblast stage. Contrary to initial expectations, arrested GATA-1(-)-definitive proerythroblasts express GATA target genes at normal levels. Transcripts of the related factor GATA-2 are remarkably elevated in GATA-1- proerythroblasts. These findings imply substantial interchangeability of GATA factors in vivo and suggest that GATA-1 normally serves to repress GATA-2 during erythropoiesis. The approach used here is a paradigm for the phenotypic analysis of targeted mutations affecting hematopoietic development. PMID: 7926723 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 57: Brain Res Mol Brain Res. 1994 Apr;23(1-2):100-10. Temporal and spatial changes in GATA transcription factor expression are coincident with development of the chicken optic tectum. Kornhauser JM, Leonard MW, Yamamoto M, LaVail JH, Mayo KE, Engel JD. Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, IL 60208-3500. The molecular mechanisms specifying patterns of gene expression in the vertebrate brain, which in turn determine the developmental fates of specific neurons, are yet to be clearly defined. Individual members of a recently identified family of transcriptional regulatory proteins, the GATA factors, are required for the differentiation of certain hematopoietic cell lineages. We show here that two of the members of this gene family, GATA-2 and GATA-3, are expressed within discrete cell populations of the chicken optic tectum during embryogenesis, and that they have highly restricted patterns of expression in the developing chicken brain. Furthermore, the induction of GATA factor expression within specific cell layers parallels the well established spatial (rostral to caudal) and temporal pattern of optic tectum development. The observation that both the timing of appearance and the localization of expression of GATA-2 and GATA-3 are correlated with optic tectum development suggest that these transcription factors may be associated with the initiation of gene transcription required for the determination of specific neuronal fates within visual areas of the vertebrate brain. PMID: 8028475 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 58: Development. 1993 Oct;119(2):519-31. Expression of the chicken GATA factor family during early erythroid development and differentiation. Leonard MW, Lim KC, Engel JD. Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL 60208-3500. The DNA motif WGATAR has been identified within transcriptional regulatory domains of globin and other erythroid-specific genes and the activator proteins that bind to this regulatory element, the GATA factors, belong to a multi-gene family that is expressed in chicken erythroid cells. Here we show that, as in chickens, multiple members of the GATA factor family are expressed in human and murine erythroid cells. During the early stages of chicken embryogenesis (well before blood island formation), each of the GATA family members is transcribed with a unique temporal and spatial pattern. In the primitive erythroid lineage, transcription of the embryonic epsilon-globin gene parallels GATA-1 expression while the switch to beta-globin transcription in definitive erythroid cells is directly preceded by a pronounced increase in GATA-3 accumulation. The timing and pattern of expression of these different mRNAs during avian erythroid development and differentiation suggests that temporally regulated changes in GATA factor expression are required for vertebrate hematopoiesis. PMID: 8287800 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 59: Blood. 1993 Sep 1;82(5):1493-501. Megakaryocytic differentiation induced in 416B myeloid cells by GATA-2 and GATA-3 transgenes or 5-azacytidine is tightly coupled to GATA-1 expression. Visvader J, Adams JM. Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Australia. The GATA 'zinc-finger' transcription factors are thought to have important roles in the control of hematopoiesis. GATA-1 and GATA-2 are found in the erythroid, mast cell, and megakaryocytic lineages, and GATA-3 in T lymphocytes. GATA-1 is required for erythroid development and has recently been shown by gene transfer to direct megakaryocytic differentiation of the primitive myeloid cell line 416B. Here we show that enforced expression in 416B cells of either the GATA-2 or GATA-3 gene also induces megakaryocytic differentiation, as assessed by cellular morphology, acetylcholinesterase activity, polyploid DNA content, and loss of Mac-1 expression. No erythroid or mast cell differentiation was found. Unexpectedly, the level of endogenous GATA-1 mRNA had increased 20- to 30-fold among the transfectants, whereas that of GATA-2 mRNA was unaltered and endogenous GATA-3 transcripts remained undetectable. This finding suggests that GATA-2 and GATA-3 lie upstream of GATA-1 in a regulatory hierarchy and that, in 416B cells, GATA-1 may mediate the phenotypic changes induced by GATA-2 or GATA-3. Furthermore, 416B cells treated with the DNA demethylating agent 5-azacytidine underwent megakaryocytic differentiation accompanied by a marked increase in the level of GATA-1 mRNA but not that of GATA-2 or GATA-3. These results strongly implicate GATA factors in megakaryocytic differentiation and suggest that, at least for 416B cells, GATA-1 is a dominant regulator of maturation along this lineage. PMID: 7689871 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 60: Mol Cell Biol. 1993 Jul;13(7):4011-22. DNA-binding specificities of the GATA transcription factor family. Ko LJ, Engel JD. Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208-3500. Members of the GATA family of transcription factors, which are related by a high degree of amino acid sequence identity within their zinc finger DNA-binding domains, each show distinct but overlapping patterns of tissue-restricted expression. Although GATA-1, -2, and -3 have been shown to recognize a consensus sequence derived from regulatory elements in erythroid cell-specific genes, WGATAR (in which W indicates A/T and R indicates A/G), the potential for more subtle differences in the binding preferences of each factor has not been previously addressed. By employing a binding selection and polymerase chain reaction amplification scheme with randomized oligonucleotides, we have determined the binding-site specificities of bacterially expressed chicken GATA-1, -2, and -3 transcription factors. Whereas all three GATA factors bind an AGATAA erythroid consensus motif with high affinity, a second, alternative consensus DNA sequence, AGATCTTA, is also recognized well by GATA-2 and GATA-3 but only poorly by GATA-1. These studies suggest that all three GATA factors are capable of mediating transcriptional effects via a common erythroid consensus DNA-binding motif. Furthermore, GATA-2 and GATA-3, because of their distinct expression patterns and broader DNA recognition properties, may be involved in additional regulatory processes beyond those of GATA-1. The definition of an alternative GATA-2-GATA-3 consensus sequence may facilitate the identification of new target genes in the further elucidation of the roles that these transcription factors play during development. PMID: 8321208 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 61: Mol Cell Biol. 1993 Jul;13(7):3999-4010. DNA-binding specificity of GATA family transcription factors. Merika M, Orkin SH. Division of Hematology/Oncology, Children's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts. GATA-binding proteins constitute a family of transcription factors that recognize a target site conforming to the consensus WGATAR (W = A or T and R = A or G). Here we have used the method of polymerase chain reaction-mediated random site selection to assess in an unbiased manner the DNA-binding specificity of GATA proteins. Contrary to our expectations, we show that GATA proteins bind a variety of motifs that deviate from the previously assigned consensus. Many of the nonconsensus sequences bind protein with high affinity, equivalent to that of conventional GATA motifs. By using the selected sequences as probes in the electrophoretic mobility shift assay, we demonstrate overlapping, but distinct, sequence preferences for GATA family members, specified by their respective DNA-binding domains. Furthermore, we provide additional evidence for interaction of amino and carboxy fingers of GATA-1 in defining its binding site. By performing cotransfection experiments, we also show that transactivation parallels DNA binding. A chimeric protein containing the finger domain of areA and the activation domains of GATA-1 is capable of activating transcription in mammalian cells through GATA motifs. Our findings suggest a mechanism by which GATA proteins might selectively regulate gene expression in cells in which they are coexpressed. PMID: 8321207 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 62: Blood. 1993 Jun 15;81(12):3234-41. Expression of mRNA for the GATA-binding proteins in human eosinophils and basophils: potential role in gene transcription. Zon LI, Yamaguchi Y, Yee K, Albee EA, Kimura A, Bennett JC, Orkin SH, Ackerman SJ. Division of Hematology, Children's Hospital, Boston, MA 02115. The expression of the hematopoietic transcription factors GATA-1, GATA-2, and GATA-3 was studied in eosinophils and basophils. Eosinophils express mRNA for GATA-1, GATA-2, and GATA-3. Basophils express GATA-2 and GATA-3. Treatment of HL-60 eosinophilic sublines with either interleukin-5 or butyric acid increased the expression of GATA-1 mRNA concomitant with the expression of eosinophil-specific genes, whereas levels of GATA-2 mRNA remained relatively constant. The presence of mRNA for these proteins in eosinophils and basophils suggests that gene transcription in these lineages may be regulated by GATA-binding proteins. PMID: 8507862 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 63: Genes Dev. 1993 Jun;7(6):1097-109. Ectopic expression of a conditional GATA-2/estrogen receptor chimera arrests erythroid differentiation in a hormone-dependent manner. Briegel K, Lim KC, Plank C, Beug H, Engel JD, Zenke M. Institute of Molecular Pathology (IMP), Vienna, Austria. The GATA factors are a family of transcriptional regulatory proteins in eukaryotes that share extensive homology in their DNA-binding domains. One enigmatic aspect of GATA factor expression is that several GATA proteins, which ostensibly share the same DNA-binding site specificity, are coexpressed in erythroid cells. To elucidate the roles of individual GATA factors in erythropoiesis, conditional alleles of GATA-1, GATA-2, and GATA-3 were prepared by fusing each of the factors to the hormone-binding domain of the human estrogen receptor (ER). These GATA/ER chimeric factors were shown to be hormone-inducible trans-activating proteins in transient transfection assays. When stably introduced into primary erythroblasts or conditionally transformed erythroid progenitors cells, exogenous GATA-2/ER promoted proliferation and inhibited terminal differentiation in an estrogen-dependent manner. These phenotypic effects are specifically attributable to the action of ectopically expressed GATA-2/ER because erythroblasts expressing exogenous GATA-2 are constitutively arrested in differentiation and because erythroid progenitors expressing either Gal/ER or GATA-3/ER do not display a hormone-responsive block in differentiation. Thus, the GATA-2 transcription factor appears to play a role in regulating the self-renewal capacity of early erythroid progenitor cells. PMID: 8504932 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 64: Blood. 1992 Aug 1;80(3):575-81. GATA-binding transcription factors in hematopoietic cells. Orkin SH. Division of Hematology/Oncology, Children's Hospital, Boston, MA 02115. Publication Types: Review Review, Tutorial PMID: 1638017 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 65: J Biol Chem. 1991 Dec 5;266(34):22948-53. GATA-binding transcription factors in mast cells regulate the promoter of the mast cell carboxypeptidase A gene. Zon LI, Gurish MF, Stevens RL, Mather C, Reynolds DS, Austen KF, Orkin SH. Department of Pediatrics, Harvard Medical School, Children's Hospital, Boston, Massachusetts 02115. The transcription factors GATA-1, GATA-2, and GATA-3 were found to be expressed in several mouse and rat mast cell lines that contain mast cell carboxypeptidase A (MC-CPA) and other proteases in their cytoplasmic granules. GATA-1 mRNA was not detected in P815 cells, an immature mouse mastocytoma-derived cell line that lacks electron-dense granules and has low levels of secretory granule proteases. Because the 5'-flanking regions of the mouse and human MC-CPA genes contained a conserved GATA-binding motif 51 base pairs upstream of their translation initiation sites, the ability of GATA-binding proteins to regulate the promoter activity of the MC-CPA gene was examined in rat basophilic leukemia cells, mouse P815 cells, and transfected mouse P815 cells that expressed GATA-1. In all three mast cell lines, the promoter activity of the MC-CPA gene depended on the GATA binding site. GATA-1, GATA-2, and GATA-3 are thus the first DNA-binding proteins identified in mast cells which regulate the promoter activity of a gene that encodes a secretory granule protease. PMID: 1744088 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 66: Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10642-6. Expression of GATA-binding proteins during embryonic development in Xenopus laevis. Zon LI, Mather C, Burgess S, Bolce ME, Harland RM, Orkin SH. Division of Hematology-Oncology, Children's Hospital, Boston, MA. Proteins that recognize the core sequence GATA are important regulators of hematopoietic-specific gene transcription. We have characterized cDNAs encoding the Xenopus laevis homologues of three related transcription factors, designated GATA-1, -2, and -3. Comparative sequence analysis reveals strong conservation of the zinc-finger DNA-binding domain among all vertebrate GATA-binding proteins. GATA-2 and GATA-3 polypeptides are homologous throughout their entire sequences, whereas GATA-1 sequence is conserved only in the region responsible for DNA binding. In Xenopus, RNAs encoding GATA-binding proteins are expressed in both larval and adult erythroid cells. GATA-1, -2, and -3 RNAs are first detectable in early gastrula (Nieuwkoop developmental stage 11). This is earlier than the appearance of the early larval alpha T1 globin RNA (stage 15), beta T1 globin RNA (stage 26), or blood island formation (stage 30). The expression of GATA-1, -2, and -3 in early development may signal an early commitment of mesoderm to form hematopoietic tissue. PMID: 1961730 [PubMed - indexed for MEDLINE] ---------------------------------------------------------------