Abstract
Chromatin remodeling is an important step in promoter activation during cellular lineage commitment and differentiation. We show that the ability of the C/EBPalpha transcription factor to direct adipocyte differentiation of uncommitted fibroblast precursors and to activate SWI/SNF-dependent myeloid-specific genes depends on a domain, C/EBPalpha transactivation element III (TE-III), that binds the SWI/SNF chromatin remodeling complex. TE-III collaborates with C/EBPalpha TBP/TFIIB interaction motifs during induction of adipogenesis and adipocyte-specific gene expression. These results indicate that C/EBPalpha acts as a lineage-instructive transcription factor through SWI/SNF-dependent modification of the chromatin structure of lineage-specific genes, followed by direct promoter activation via recruitment of the basal transcription-initiation complex, and provide a mechanism by which C/EBPalpha can mediate differentiation along multiple cellular lineages.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Adipocytes / cytology*
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Amino Acid Sequence
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Animals
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Binding Sites
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CCAAT-Enhancer-Binding Protein-alpha / chemistry
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CCAAT-Enhancer-Binding Protein-alpha / genetics
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CCAAT-Enhancer-Binding Protein-alpha / metabolism*
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Cell Differentiation*
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Cell Lineage
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Chromatin / chemistry
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Chromatin / metabolism
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Conserved Sequence / genetics
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DNA Helicases
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Erythroblasts
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Fibroblasts
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Gene Expression Regulation
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Macromolecular Substances
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Mice
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Molecular Sequence Data
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Mutation / genetics
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Nuclear Proteins*
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Promoter Regions, Genetic / genetics
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Protein Binding
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Protein Structure, Tertiary
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Quail
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RNA, Messenger / metabolism
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Rats
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Substrate Specificity
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TATA-Box Binding Protein
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Transcription Factor TFIIB
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Transcription Factors / chemistry
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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CCAAT-Enhancer-Binding Protein-alpha
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Chromatin
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DNA-Binding Proteins
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Macromolecular Substances
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Nuclear Proteins
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RNA, Messenger
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Smarca2 protein, mouse
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TATA-Box Binding Protein
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Transcription Factor TFIIB
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Transcription Factors
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Smarca4 protein, mouse
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DNA Helicases