1: Mol Cell Biol. 2003 Apr;23(8):2749-61. NF-kappa B-dependent assembly of an enhanceosome-like complex on the promoter region of apoptosis inhibitor Bfl-1/A1. Edelstein LC, Lagos L, Simmons M, Tirumalai H, Gelinas C. Center for Advanced Biotechnology and Medicine and Graduate Program in Biotechnology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA. Expression of the prosurvival Bcl-2 homologue Bfl-1/A1 is induced by NF-kappa B-activating stimuli, while B and T cells from c-rel knockout mice show an absolute defect in bfl-1/a1 gene activation. Here, we demonstrate NF-kappa B-dependent assembly of an enhanceosome-like complex on the promoter region of bfl-1. Binding of NF-kappa B subunit c-Rel to DNA nucleated the concerted binding of transcription factors AP-1 and C/EBP beta to the 5'-regulatory region of bfl-1. Optimal stability of the complex was dependent on proper orientation and phasing of the NF-kappa B site. Chromatin immunoprecipitation analyses demonstrated that T-cell activation triggers in vivo binding of endogenous c-Rel, c-Jun, C/EBP beta, and HMG-IC to the bfl-1 regulatory region, coincident with selective recruitment of coactivators TAFII250 and p300, SWI/SNF chromatin remodeling factor component BRG-1, and basal transcription factors TATA-binding protein (TBP) and TFIIB, as well as hyperacetylation of histones H3 and H4. These results highlight a critical role for NF-kappa B in bfl-1 transcription and point to the need for a complex and precise regulatory network to control bfl-1 expression. To our knowledge, this is the first demonstration of enhanceosome-mediated regulation of a cell death inhibitor. PMID: 12665576 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 2: J Biol Chem. 2001 Jul 20;276(29):27203-6. Epub 2001 May 22. Invariant chain induces B cell maturation by activating a TAF(II)105-NF-kappaB-dependent transcription program. Matza D, Wolstein O, Dikstein R, Shachar I. Departments of Immunology and Biological Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel. Early stages of B cell development occur in the bone marrow, resulting in formation of immature B cells. From there these immature cells migrate to the spleen where they differentiate to mature cells. This final maturation step is crucial for the B cells to become responsive to antigens and to participate in the immune response. Recently, invariant chain (Ii), a major histocompatibility complex class II chaperone, as well as the transcription factors c-Rel and p65/RelA, were found to play a role in the final antigen-independent differentiation stage of B cells in the spleen. In this study, we investigated a possible link between Ii-dependent B cell maturation and the NF-kappaB pathway. Our studies indicate that Ii-induced B cell maturation involves activation of transcription mediated by the NF-kappaB p65/RelA homodimer and requires the B cell-enriched coactivator TBP-associated factor (II)105. PMID: 11371575 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 3: Mech Dev. 1999 Jun;84(1-2):3-16. Mesoderm-determining transcription in Drosophila is alleviated by mutations in TAF(II)60 and TAF(II)110. Pham AD, Muller S, Sauer F. Zentrum fur Molekulare Biologie der Universitat Heidelberg, Germany. In Drosophila, a coordinate interplay between the Rel transcription factor Dorsal and the basic Helix-Loop-Helix transcription factor Twist initiates mesoderm formation by activating the zygotic expression of mesoderm-determining genes. Here, we show that TBP-associated-factors (TAF(II)s) within the basal transcription factor TFIID mediate transcriptional activation by Dorsal and Twist. Dorsal interacts with TAF(II)110 and TAF(II)60, while Twist contacts TAF(II)110. The TAF(II):activator interactions mediate simple and synergistic transactivation by Dorsal and Twist in vitro. Mutations in TAF(II)60 or TAF(II)110 alleviate the transcription of Dorsal and Twist target genes. Gene dosage assays imply that an interplay of Dorsal and Twist with TAF(II)110 is critically required for the activation of mesoderm-determining gene expression in the Drosophila embryo. The results provide evidence that TAF(II)-subunits within the TFIID complex play an important role during the molecular events leading to initiation of mesoderm formation in Drosophila. PMID: 10473116 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 4: Mol Cell Biol. 1998 Jun;18(6):3234-44. Involvement of TFIID and USA components in transcriptional activation of the human immunodeficiency virus promoter by NF-kappaB and Sp1. Guermah M, Malik S, Roeder RG. Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, New York 10021, USA. The purified Rel/NF-kappaB (p50/p65) complex and Sp1 markedly activate transcription from the human immunodeficiency virus type 1 (HIV-1) promoter in a highly purified HeLa reconstituted transcription system. Transcriptional activation by NF-kappaB and Sp1 requires both TFIID and the USA fraction. The USA-derived coactivators PC2 and PC4 fully reconstitute the USA coactivator activity, both by repressing the basal level of transcription and by potentiating activator function to yield large increases in the levels of transcription induction. Under limiting concentrations, PC2 and PC4 also show synergistic effects. The C-terminal portion (amino acids 416 to 550) of the p65 subunit of NF-kappaB is a potent activator when assayed as a Gal fusion in the reconstituted transcription system and interacts both with TATA-binding protein (TBP) and with several human TBP-associated factors (TAFs) that include TAFII250. The p65 activation domain mediates transcription activation in the presence of partially reconstituted TFIID species that include a minimal complex containing only TBP and TAFII250. These studies also show that, like USA components, TAFs can serve both to repress TBP-mediated transcription and, following activator interactions, to reverse the repression and effect a net increase in activity. Taken together, these data underscore the importance of both TAFs and specific USA-derived coactivators for optimal activation of the HIV-1 promoter, as well as certain parallels in their overall mechanisms of action. PMID: 9584164 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 5: EMBO J. 1996 Dec 16;15(24):7079-87. The transcriptional corepressor DSP1 inhibits activated transcription by disrupting TFIIA-TBP complex formation. Kirov NC, Lieberman PM, Rushlow C. Department of Biology, New York University, New York, NY 10003, USA. Transcriptional repression of eukaryotic genes is essential for many cellular and developmental processes, yet the precise mechanisms of repression remain poorly understood. The Dorsal Switch Protein (DSP1) was identified in a genetic screen for activities which convert Dorsal into a transcriptional repressor. DSP1 shares structural homology with the HMG-1/2 family and inhibits activation by the rel transcription factors Dorsal and NF-kappaB in transfection studies. Here we investigate the mechanism of transcriptional repression by DSP1. We found that DSP1 protein can act as a potent transcriptional repressor for multiple activator families in vitro and in transfection studies. DSP1 bound directly to the TATA binding protein (TBP), and formed a stable ternary complex with TBP bound to DNA. DSP1 preferentially disrupted the DNA binding of TBP complexes containing TFIIA and displaced TFIIA from binding to TBP. Consistent with the inhibition of TFIIA-bound complexes, DSP1 was shown to inhibit activated but not basal transcription reactions in vitro. The ability of DSP1 to interact with TBP and to repress transcription was mapped to the carboxy-terminal domain which contains two HMG boxes. Our results support the model that DSP1 represses activated transcription by interfering with the binding of TFIIA, a general transcription factor implicated in activated transcription pathways. PMID: 9003783 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 6: Mol Cell Biol. 1993 Nov;13(11):6733-41. Functional interaction of the v-Rel and c-Rel oncoproteins with the TATA-binding protein and association with transcription factor IIB. Xu X, Prorock C, Ishikawa H, Maldonado E, Ito Y, Gelinas C. Center for Advanced Biotechnology and Medicine, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway 08854-5638. Rel family proteins regulate the expression of genes linked to kappa B-binding motifs. Little is known, however, of the mechanism by which they enhance transcription. We have investigated the ability of the v-Rel and c-Rel oncoproteins to interact with components of the basal transcription machinery. Here we report that both the acidic transcription activation domain mapping to the unique C terminus of chicken c-Rel and the F9 cell-specific activation region common to both v-Rel and c-Rel interact with the TATA-binding protein (TBP) and transcription factor IIB (TFIIB) in vitro and in vivo. We also demonstrate that TPB interaction with Rel activation regions leads to synergistic activation of transcription of a kappa B-linked reporter gene. Combined with the observation that the mouse c-Rel and human RelA proteins also interact with TBP and TFIIB in vitro, these results suggest that association with basal transcription factors is important for the transcriptional activities of Rel family proteins. PMID: 8413269 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 7: Nature. 1993 Sep 30;365(6445):412-9. Association between proto-oncoprotein Rel and TATA-binding protein mediates transcriptional activation by NF-kappa B. Kerr LD, Ransone LJ, Wamsley P, Schmitt MJ, Boyer TG, Zhou Q, Berk AJ, Verma IM. Molecular Biology and Virology Laboratory, Salk Institute, San Diego, California 92138. The c-Rel protein is able to associate in vitro and in vivo with the TATA-binding protein (TBP) of the TFIID complex. Coexpression of TBP with c-Rel augments transactivation from the kappa B site in Drosophila Schneider cells. DNA-binding mutants of TBP not only fail to cooperate, but they repress transactivation by c-Rel. There may be a direct communication between kappa B enhancer binding proteins and basal transcription factors which leads to enhanced transcription. PMID: 8413585 [PubMed - indexed for MEDLINE] ---------------------------------------------------------------