1: Eur J Biochem. 2001 May;268(9):2658-68. 

Regulation of human and mouse procathepsin E gene expression.

Cook M, Caswell RC, Richards RJ, Kay J, Tatnell PJ.

School of Biosciences, Cardiff University, Wales, UK.

Cathepsin E is an intracellular aspartic proteinase that is considered to have a
number of physiological roles including antigen processing. Quantitation of
procathepsin E mRNA by LightCyclertrade mark technology indicated that the gene
was transcribed in lung but not in kidney of both human and mouse origin. In
contrast, the transcript was present in mouse spleen and alveolar macrophages
but not in the counterpart tissue/cells from humans. Regulation of human and
mouse procathepsin E gene expression was shown not to be influenced by the
extent of CpG methylation but depended on the recognition of potential binding
motifs in each promoter region by transcription factors such as GATA1, PU1 and
YY1, as revealed by functional analysis using a series of promoter/luciferase
reporter gene fusion constructs. Thus the extent to which the procathepsin E
gene is expressed in a particular cell type may depend on the balance between
the effects produced by positive-acting, cell-specific transcription factors
such as GATA1 and PU1 and the negative influence of the ubiquitous YY1 factor.
In this way, the relative abundance and influence of general and cell-specific
transcription factors can govern the production of cathepsin E and thereby
account for the sporadic cell and tissue distribution of this enzyme in
different species.

PMID: 11322887 [PubMed - indexed for MEDLINE]


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2: Mamm Genome. 2000 Dec;11(12):1053-7. 

Genomic organization and mapping of mouse CDV (carnitine deficiency-associated
gene expressed in ventricle)-1 and its related CDV-1R gene.

Higashi M, Kobayashi K, Iijima M, Wakana S, Horiuchi M, Yasuda T, Yoshida G,
Kanmura Y, Saheki T.

Department of Biochemistry, Faculty of Medicine, Kagoshima University,
Sakuragaoka, Japan.

We have previously reported that CDV (carnitine deficiency-associated gene
expressed in ventricle)-1 was a downregulated gene in the hypertrophied
ventricle of carnitine-deficient juvenile visceral steatosis mice and that the
related gene (CDV-1R) showed no tissue specificity and no sensitivity to
carnitine deficiency. In the present paper, the CDV-1/1R gene was isolated from
a mouse genomic BAC library, and the genomic structure was characterized. We
found that the CDV-1/1R gene consisted of at least 19 exons and encompassed
approximately 48 kb. The splice sites conformed to the GT-AG rule, and the
CDV-1R mRNA containing 19 exons was processed. CDV-1 mRNA containing 5 exons was
constructed from the 3' half of CDV-1R. The first exon of CDV-1 consisted of the
3' side (116 bp) of intron 14 and exon 15 (87 bp) of CDV-1R. The presumed
promoter sequence for CDV-1 located in the intron 14 of CDV-1R contained the
common TATA box and consensus binding sites for various transcription factors
(Nkx-2.5, Spl, C/EBP, SRF, YY1, and CREB), which seem to play roles in the
heart-specific expression and carnitine deficiency-associated suppression of
CDV-1. In the upstream region of the CDV-1 promoter, we found two VNTRs, 13
repeats of GATA1, and 16 copies of STRE involved in yeast stress response. The
CDV-1/1R gene was located close to DSMIT68 on mouse Chromosome (Chr) 5,
corresponding to human Chr 12q24. All these data revealed that two mRNA species,
CDV-1 and CDV-1R, are expressed tissue-specifically by using promoters peculiar
to each transcript in a single gene.

PMID: 11130971 [PubMed - indexed for MEDLINE]


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3: EMBO J. 1995 Feb 15;14(4):801-9. 

GATA1 and YY1 are developmental repressors of the human epsilon-globin gene.

Raich N, Clegg CH, Grofti J, Romeo PH, Stamatoyannopoulos G.

INSERM U91, Hopital Henri Mondor, Creteil, France.

The human epsilon-globin gene is transcribed in erythroid cells only during the
embryonic stages of development. Expression of epsilon-globin gene, however, can
be maintained in adult transgenic mice following removal of DNA positioned
between -467 and -182 bp upstream of the epsilon-globin cap site. We have
identified three protein binding regions within this silencer; a CCACC motif
around -379, two overlapping motifs for YY1 and GATA around -269 and a GATA
motif around -208 and we have analyzed their function during development by
studying several mutants in transgenic mice. Mutation of the -208 GATA motif
allows high epsilon-globin transgene expression in the adult suggesting that, in
addition to its positive effects on transcription, GATA-1 also plays a negative
role in the regulation of globin gene expression during development. Repression
of epsilon gene expression in the adult also requires a functional YY1 binding
site at position -269. Finally, mutation of the -379 CCACC site results in a
small but detectable level of epsilon expression in adult erythroid cells. Thus,
multiple proteins, including GATA-1, participate in the formation of the epsilon
gene repressor complex that may disrupt the interaction between the proximal
epsilon-promoter and the locus control region (LCR) in definitive erythroid
cells.

PMID: 7882983 [PubMed - indexed for MEDLINE]


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