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PMID: 9111350 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Chicken ovalbumin upstream promoter transcription factors act as auxiliary cofactors for hepatocyte nuclear factor 4 and enhance hepatic gene expression.

Molecular and cellular biology ·Vol. 17 ·No. 5 ·1997-05-00 ·Pages 2790-7

Ktistaki E, Talianidis I

Abstract

Chicken ovalbumin upstream promoter transcription factors (COUP-TFs) strongly inhibit transcriptional activation mediated by nuclear hormone receptors, including hepatocyte nuclear factor 4 (HNF-4). COUP-TFs repress HNF-4-dependent gene expression by competition with HNF-4 for common binding sites found in several regulatory regions. Here we show that promoters, such as the HNF-1 promoter, which are recognized by HNF-4 but not by COUP-TFs are activated by COUP-TFI and COUP-TFII in conjunction with HNF-4 more than 100-fold above basal levels, as opposed to about 8-fold activation by HNF-4 alone. This enhancement was strictly dependent on an intact HNF-4 E domain. In vitro and in vivo evidence suggests that COUP-TFs enhance HNF-4 activity by a mechanism that involves their physical interaction with the amino acid 227 to 271 region of HNF-4. Our results indicate that in certain promoters, COUP-TFs act as auxiliary cofactors for HNF-4, orienting the HNF-4 activation domain in a more efficient configuration to achieve enhanced transcriptional activity. These findings provide new insights into the regulatory functions of COUP-TFs, suggesting their involvement in the initial activation and subsequent high-level expression of hepatic regulators, as well as in the positive and negative modulation of downstream target genes.

MeSH Terms
Animals Basic Helix-Loop-Helix Leucine Zipper Transcription Factors COS Cells COUP Transcription Factor I COUP Transcription Factor II COUP Transcription Factors Caco-2 Cells Chickens DNA-Binding Proteins/genetics,metabolism Gene Expression Regulation Hepatocyte Nuclear Factor 1 Hepatocyte Nuclear Factor 1-alpha Hepatocyte Nuclear Factor 1-beta Hepatocyte Nuclear Factor 4 Humans Liver/metabolism Nuclear Proteins/genetics Phosphoproteins/metabolism Promoter Regions, Genetic Receptors, Cell Surface/metabolism Receptors, Glucocorticoid/metabolism Receptors, Steroid Transcription Factors/genetics,metabolism Tumor Cells, Cultured
Chemicals
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors COUP Transcription Factor I COUP Transcription Factor II COUP Transcription Factors DNA-Binding Proteins HNF1A protein, human HNF1B protein, human Hepatocyte Nuclear Factor 1-alpha Hepatocyte Nuclear Factor 4 MLX protein, human NR2F1 protein, human NR2F2 protein, human Nuclear Proteins Phosphoproteins Receptors, Cell Surface Receptors, Glucocorticoid Receptors, Steroid Transcription Factors Hepatocyte Nuclear Factor 1 Hepatocyte Nuclear Factor 1-beta
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Ktistaki E
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, Herakleion, Crete, Greece.
Talianidis I
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.17.5.2790
Published
1997-05-00
Pages
2790-7
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC232130
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.17.5.2790 PMC Full Text View journal details
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