Transcriptional activation by hepatocyte nuclear factor-1 requires synergism between multiple coactivator proteins.
Hepatocyte nuclear factor-1 (HNF-1) plays an important role in the regulation of a large number of genes expressed in the liver, kidney, and pancreatic beta-cells. In exploring the molecular mechanism involved in HNF-1-dependent gene activation in the in vivo chromatin context, we found that HNF-1 can physically interact with the ... histone acetyltransferases (HATs) CREB-binding protein (CBP), p300/CBP-associated factor (P/CAF), Src-1, and RAC3. The transcriptional activation potential of HNF-1 on a genome integrated promoter was strictly dependent on the synergistic action of CBP and P/CAF, which can independently interact with the N-terminal and C-terminal domain of HNF-1, respectively. Moreover, the HAT activity of both coactivators was important, as opposed to the selective requirement for the HAT activity of P/CAF in activation from a transiently transfected reporter. Interaction of CBP with the N-terminal domain of HNF-1 greatly increased the binding affinity for P/CAF with the C-terminal activation domain, which may represent the molecular basis for the observed functional synergism. The results support a model that involves the combined action of multiple coactivators recruited by HNF-1, which activate transcription by coupling nucleosome modification and recruitment of the general transcription machinery.
Mesh Terms:
3T3 Cells, Acetyltransferases, Animals, COS Cells, CREB-Binding Protein, Cell Cycle Proteins, Chromatin, DNA-Binding Proteins, Gene Expression Regulation, Hepatocyte Nuclear Factor 1, Hepatocyte Nuclear Factor 1-alpha, Hepatocyte Nuclear Factor 1-beta, Histone Acetyltransferases, Mice, Nuclear Proteins, Nuclear Receptor Coactivator 1, Nuclear Receptor Coactivator 3, Plasmids, Precipitin Tests, Promoter Regions, Genetic, Protein Binding, Saccharomyces cerevisiae Proteins, Trans-Activators, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Transfection, p300-CBP Transcription Factors
3T3 Cells, Acetyltransferases, Animals, COS Cells, CREB-Binding Protein, Cell Cycle Proteins, Chromatin, DNA-Binding Proteins, Gene Expression Regulation, Hepatocyte Nuclear Factor 1, Hepatocyte Nuclear Factor 1-alpha, Hepatocyte Nuclear Factor 1-beta, Histone Acetyltransferases, Mice, Nuclear Proteins, Nuclear Receptor Coactivator 1, Nuclear Receptor Coactivator 3, Plasmids, Precipitin Tests, Promoter Regions, Genetic, Protein Binding, Saccharomyces cerevisiae Proteins, Trans-Activators, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Transfection, p300-CBP Transcription Factors
J. Biol. Chem.
Date: Apr. 28, 2000
PubMed ID: 10777539
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