Source:http://linkedlifedata.com/resource/pubmed/id/10085149
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
13
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pubmed:dateCreated |
1999-4-29
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pubmed:abstractText |
Hepatocyte nuclear factor-4 (HNF-4) is a liver-enriched transcription factor that is crucial in the regulation of a large number of genes involved in glucose, cholesterol, and fatty acid metabolism and in determining the hepatic phenotype. We have previously shown that HNF-4 contains transcription activation functions at the N terminus (AF-1) and the C terminus (AF-2) which work synergistically to confer full HNF-4 activity. Here, we show that HNF-4 recruits the CREB-binding protein (CBP) coactivator on promoters of genes that contain functional HNF-4 sites. HNF-4 interacts with the N-terminal region of CBP (amino acids 1-771) and the C-terminal region of CBP (amino acids 1812-2441). The two activating functions of HNF-4, AF-1 and AF-2, interact with the N terminus and the N and C terminus of CBP, respectively. In addition, we show that in contrast to the other nuclear hormone receptors the interaction between HNF-4 and CBP is ligand-independent. Recruitment of CBP by HNF-4 results in an enhancement of the transcriptional activity of the latter. CBP does not activate gene expression in the absence of HNF-4, and dominant negative forms of HNF-4 prevent transcriptional activation by CBP, suggesting that the mere recruitment of CBP by HNF-4 is not sufficient for enhancement of gene expression. These findings demonstrate that CBP acts as a transcriptional coactivator for HNF-4 and provide new insights into the regulatory function of HNF-4.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Apolipoprotein C-III,
http://linkedlifedata.com/resource/pubmed/chemical/Apolipoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Apolipoproteins C,
http://linkedlifedata.com/resource/pubmed/chemical/CREB-Binding Protein,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Hepatocyte Nuclear Factor 4,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
26
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pubmed:volume |
274
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
9013-21
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:10085149-Apolipoprotein C-III,
pubmed-meshheading:10085149-Apolipoproteins,
pubmed-meshheading:10085149-Apolipoproteins C,
pubmed-meshheading:10085149-CREB-Binding Protein,
pubmed-meshheading:10085149-DNA-Binding Proteins,
pubmed-meshheading:10085149-Gene Expression Regulation,
pubmed-meshheading:10085149-Genes, Reporter,
pubmed-meshheading:10085149-Hepatocyte Nuclear Factor 4,
pubmed-meshheading:10085149-Liver,
pubmed-meshheading:10085149-Mutation,
pubmed-meshheading:10085149-Nuclear Proteins,
pubmed-meshheading:10085149-Phosphoproteins,
pubmed-meshheading:10085149-Promoter Regions, Genetic,
pubmed-meshheading:10085149-Trans-Activators,
pubmed-meshheading:10085149-Transcription Factors,
pubmed-meshheading:10085149-Transcriptional Activation,
pubmed-meshheading:10085149-Transfection,
pubmed-meshheading:10085149-Tumor Cells, Cultured
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pubmed:year |
1999
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pubmed:articleTitle |
CREB-binding protein is a transcriptional coactivator for hepatocyte nuclear factor-4 and enhances apolipoprotein gene expression.
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pubmed:affiliation |
Department of Medicine, Section of Molecular Genetics, Cardiovascular Institute, Boston University School of Medicine, Center for Advanced Biomedical Research, Boston, Massachusetts 02118-2394, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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