Abstract
We analyzed the order of recruitment of factors to the HNF-4alpha regulatory regions upon the initial activation of the gene during enterocyte differentiation. An initially independent assembly of regulatory complexes at the proximal promoter and the upstream enhancer regions was followed by the tracking of the entire DNA-protein complex formed on the enhancer along the intervening DNA until it encountered the proximal promoter. This movement correlated with a unidirectional spreading of histone hyperacetylation. Transcription initiation coincided with the formation of a stable enhancer-promoter complex and remodeling of the nucleosome situated at the transcription start site. The results provide experimental evidence for the involvement of a dynamic process culminating in enhancer-promoter communication during long-distance gene activation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Cell Differentiation / genetics*
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Chromatin / drug effects
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Chromatin / genetics*
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Chromatin / ultrastructure
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Cross-Linking Reagents / pharmacology
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DNA-Binding Proteins*
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Enhancer Elements, Genetic*
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Formaldehyde / pharmacology
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Gene Expression Regulation*
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Gene Expression Regulation, Neoplastic
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Hepatocyte Nuclear Factor 4
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Humans
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Intestinal Mucosa / physiology
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Phosphoproteins / genetics*
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Promoter Regions, Genetic*
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Regulatory Sequences, Nucleic Acid*
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Transcription Factors / genetics*
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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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Chromatin
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Cross-Linking Reagents
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DNA-Binding Proteins
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HNF4A protein, human
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Hepatocyte Nuclear Factor 4
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MLX protein, human
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Phosphoproteins
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Transcription Factors
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Formaldehyde