The Role of Cis-Acting Promoter Elements in Tissue-Specific Albumin Gene Expression

Maire, Pascal; Wuarin, Jérôme; Schibler, Ulrich

doi:10.1126/science.2711183

Cited by 333 publications

(223 citation statements)

References 34 publications

Supporting

Mentioning

214

Contrasting

Unclassified

Order By: Relevance

“…4C, self). Interestingly, however, competition with two distinct C/EBP-binding sites derived from the D site of the albumin promoter (31) or from the A site of the hemopexin promoter (32) could abolish all bands except the one corresponding to complex 3 that appeared therefore to be unique to the COX-2 C/EBP1 site. Since complex 3 was also not supershifted by any of the anti-C/EBP antibodies used (Fig.…”

Section: Dna-protein Interactions On the Cox-2 Promoter Are Onlymentioning

confidence: 99%

The Transcription Factor C/EBPβ Is Essential for Inducible Expression of the cox-2 Gene in Macrophages but Not in Fibroblasts

Gorgoni¹,

Caivano²,

Arizmendi³

et al. 2001

Journal of Biological Chemistry

105

View full text Add to dashboard Cite

Cyclooxygenase-2 (COX-2) is the rate-limiting enzyme for the inducible synthesis of prostaglandins, and its up-regulated activity is thought to play a pathological role in diseases such as inflammatory bowel disease, rheumatoid arthritis, and cancer. Regulation of COX-2 expression is complex and appears to involve diversified mechanisms in different cell types and conditions. Here we make use of immortalized macrophages and fibroblasts that we have generated from C/EBP␤-deficient mice to directly test and compare the specific role played by this factor in inducible COX-2 expression in these two cell types. We could demonstrate that COX-2 mRNA induction and promoter activity were profoundly impaired in C/EBP␤ ؊/؊ macrophages and could be rescued by expression of C/EBP␤. The obligatory role of C/EBP␤ in COX-2 expression appeared to be mediated exclusively by the C/EBP element located at positions ؊138/؊130 of the murine cox-2 promoter, and did not involve altered activity at the level of the other promoter elements described previously (the ؊402/؊392 NF-B site, the ؊59/؊48 CRE/E box element, and a potential second C/EBP site located at positions ؊93/؊85). In contrast, COX-2 induction was completely normal in C/EBP␤-deficient fibroblasts, thus highlighting the diversity of cell-specific molecular mechanisms in determining inducible COX-2 expression and prostaglandins production.

show abstract

Section: Dna-protein Interactions On the Cox-2 Promoter Are Onlymentioning

confidence: 99%

The Transcription Factor C/EBPβ Is Essential for Inducible Expression of the cox-2 Gene in Macrophages but Not in Fibroblasts

Gorgoni¹,

Caivano²,

Arizmendi³

et al. 2001

Journal of Biological Chemistry

105

View full text Add to dashboard Cite

show abstract

“…These elements have been shown to be the binding sites of a liver-enriched transcription factor, HNF1 (also called LF-B1 and APF) (3-6, 12, 31). Mutations of the AT-rich element cause drastic reduction of liver-specific transcriptional activity both in vitro and in vivo (21,28,33,42), indicating that the AT-rich element and HNF1 play a crucial role in liver-specific promoter activation.…”

mentioning

confidence: 99%

ATBF1, a multiple-homeodomain zinc finger protein, selectively down-regulates AT-rich elements of the human alpha-fetoprotein gene.

Yasuda¹,

Mizuno²,

Tamaoki³

et al. 1994

Mol. Cell. Biol.

View full text Add to dashboard Cite

ATBF1 is a 306-kDa protein containing four homeodomains, 17 zinc finger motifs, and several segments potentially involved in transcriptional regulation (T. Morinaga, H. Yasuda, T. Hashimoto, K. Higashio, and T. Tamaoki, Mol. Cell. Biol. 11:6041-6049, 1991). At least one of the homeodomains of ATBF1 binds to an AT-rich element in the human a-fetoprotein (AFP) enhancer (enhancer AT motif). In the present work, we analyzed the transcriptional regulatory activity of ATBF1 with respect to the enhancer AT motif and similar AT-rich elements in the human AFP promoter and the human albumin promoter and enhancer. Gel retardation assays showed that ATBF1 binds to the AFP enhancer AT motif efficiently; however, it binds weakly or not at all to other AT-rich elements in the AFP and albumin regulatory regions studied. Alterations of the enhancer AT motif by site-specific mutagenesis resulted in the loss of binding of ATBF1. Cotransfection experiments with an ATBF1 expression plasmid and the chloramphenicol acetyltransferase (CAT) gene fused to AFP promoter or enhancer fragments showed that ATBF1 suppressed the activity of AFP enhancer and promoter regions containing AT-rich elements. This suppression was reduced when the mutated AT motifs with low affinity to ATBF1 were linked to the CAT gene. The ATBF1 suppression of AFP promoter and enhancer activities appeared to be due, at least in part, to competition between ATBF1 and HNF1 for the same binding site. In contrast to the AFP promoter and enhancer, the albumin promoter and enhancer were not affected by ATBF1, although they contain homologous AT-rich elements. These results show that ATBF1 is able to distinguish AFP and albumin AT-rich elements, leading to selective suppression of the AFP promoter and enhancer activities.The regulatory regions of all genes so far studied contain multiple cis-acting elements which interact with trans-acting factors (22,32). Liver-specific gene expression is also achieved through a combinatorial action of regulatory DNA elements and interacting transcription factors (20,21,30). One characteristic feature of a number of liver-specific promoters is the presence of DNA sequences having a well-organized array of 10 to 11 adenine (A) and thymine (T) residues sandwiched by a guanine (G) and a cytosine (C) (AT-rich element) (4-7, 11, 15, 23, 26, 40). These elements have been shown to be the binding sites of a liver-enriched transcription factor, HNF1 (also called LF-B1 and APF) (3-6, 12, 31). Mutations of the AT-rich element cause drastic reduction of liver-specific transcriptional activity both in vitro and in vivo (21, 28, 33, 42), indicating that the AT-rich element and HNF1 play a crucial role in liver-specific promoter activation.In the promoters of a-fetoprotein (AFP) genes of mice, rats, and humans, two HNF1-binding sites are conserved. In the enhancers, on the other hand, the AT-rich element is present in the human AFP gene but not in the mouse and rat genes (13). The human AFP enhancer AT motif is also unique in that HNF1 binds to it 10-fold...

show abstract

“…Hepatocyte nuclear factor-1 (HNF-1) (Courtois et al 1987), also called APF (Cereghini et al 1988), LFB1 (Hardon et al 1988), HP (Schorpp et al 1988), and A box factor (Maire et al 1989), is a homeo domain-containing protein that acts as a transcriptional activator in vivo and in vitro to regulate the expression of a large group of genes that have the common characteristic of being expressed in hepatocytes . Consistent with the presence of a homeo domain and sequences related to the POU-specific region {Frain et al 1989;Baumhueter et al 1990), HNF-1 has been suggested to play a role in establishing the hepatocyte phenotype.…”

mentioning

confidence: 99%

HNF-1 alpha and HNF-1 beta (vHNF-1) share dimerization and homeo domains, but not activation domains, and form heterodimers in vitro.

Mendel¹,

Hansen²,

Graves³

et al. 1991

Genes Dev.

294

218

View full text Add to dashboard Cite

show abstract

The Role of Cis-Acting Promoter Elements in Tissue-Specific Albumin Gene Expression

Cited by 333 publications

References 34 publications

The Transcription Factor C/EBPβ Is Essential for Inducible Expression of the cox-2 Gene in Macrophages but Not in Fibroblasts

The Transcription Factor C/EBPβ Is Essential for Inducible Expression of the cox-2 Gene in Macrophages but Not in Fibroblasts

ATBF1, a multiple-homeodomain zinc finger protein, selectively down-regulates AT-rich elements of the human alpha-fetoprotein gene.

HNF-1 alpha and HNF-1 beta (vHNF-1) share dimerization and homeo domains, but not activation domains, and form heterodimers in vitro.

Contact Info

Product

Resources

About