Cooperation between C/EBPalpha TBP/TFIIB and SWI/SNF recruiting domains is required for adipocyte differentiation.
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.
Pedersen
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TA
Laboratory of Gene Therapy Research, Copenhagen University Hospital, 2100 Copenhagen, Denmark.
Kowenz-Leutz
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E
Leutz
A
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Nerlov
C
C
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D019070:Cell Lineage; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D017124:Conserved Sequence / Q000235:genetics; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004900:Erythroblasts; D005347:Fibroblasts; D005786:Gene Expression Regulation; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011784:Quail; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013379:Substrate Specificity; D035181:TATA-Box Binding Protein; D035581:Transcription Factor TFIIB; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D022763:CCAAT-Enhancer-Binding Protein-alpha; D002843:Chromatin; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D012333:RNA, Messenger; C499503:Smarca2 protein, mouse; D035181:TATA-Box Binding Protein; D035581:Transcription Factor TFIIB; D014157:Transcription Factors; C513194:Smarca4 protein, mouse; D004265:DNA Helicases