Abstract
Hepatocyte nuclear factors 1 and 4 (HNF-1 and HNF-4) are liver-enriched transcription factors that function in the regulation of several liver-specific genes. HNF-1 activates genes containing promoters with HNF-1 binding sites. However, this factor negatively regulates its own expression and that of other HNF-4-dependent genes that lack HNF-1 binding sites in their promoter region. This repression is exerted by a direct interaction of HNF-1 with AF2, the main activation domain of HNF-4. The dual functions of gene activation and repression suggest that HNF-1 is a global regulator of the transcriptional network involved in the maintenance of hepatocyte-specific phenotype.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Binding Sites
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COS Cells
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DNA-Binding Proteins*
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Gene Expression Regulation*
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Hepatocyte Nuclear Factor 1
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Hepatocyte Nuclear Factor 1-alpha
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Hepatocyte Nuclear Factor 1-beta
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Hepatocyte Nuclear Factor 4
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Humans
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Liver / cytology
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Liver / metabolism*
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Phosphoproteins / genetics
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Phosphoproteins / metabolism
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Promoter Regions, Genetic
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Recombinant Fusion Proteins / metabolism
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Transcription Factors / genetics*
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Transcription Factors / metabolism*
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Transcriptional Activation
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Tumor Cells, Cultured
Substances
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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DNA-Binding Proteins
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HNF1A protein, human
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HNF1B protein, human
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Hepatocyte Nuclear Factor 1-alpha
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Hepatocyte Nuclear Factor 4
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MLX protein, human
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Nuclear Proteins
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Phosphoproteins
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RNA, Messenger
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Recombinant Fusion Proteins
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Transcription Factors
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Hepatocyte Nuclear Factor 1
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Hepatocyte Nuclear Factor 1-beta