Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
1999-4-29
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
274
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9013-21
pubmed:dateRevised
2008-11-21
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
pubmed:year
1999
pubmed:articleTitle
CREB-binding protein is a transcriptional coactivator for hepatocyte nuclear factor-4 and enhances apolipoprotein gene expression.
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.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't