Cooperation between C/EBPalpha TBP/TFIIB and SWI/SNF recruiting domains is required for adipocyte differentiation

Genes Dev. 2001 Dec 1;15(23):3208-16. doi: 10.1101/gad.209901.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Adipocytes / cytology*
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • CCAAT-Enhancer-Binding Protein-alpha / chemistry
  • CCAAT-Enhancer-Binding Protein-alpha / genetics
  • CCAAT-Enhancer-Binding Protein-alpha / metabolism*
  • Cell Differentiation*
  • Cell Lineage
  • Chromatin / chemistry
  • Chromatin / metabolism
  • Conserved Sequence / genetics
  • DNA Helicases
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Erythroblasts
  • Fibroblasts
  • Gene Expression Regulation
  • Macromolecular Substances
  • Mice
  • Molecular Sequence Data
  • Mutation / genetics
  • Nuclear Proteins*
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Protein Structure, Tertiary
  • Quail
  • RNA, Messenger / metabolism
  • Rats
  • Substrate Specificity
  • TATA-Box Binding Protein
  • Transcription Factor TFIIB
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • CCAAT-Enhancer-Binding Protein-alpha
  • Chromatin
  • DNA-Binding Proteins
  • Macromolecular Substances
  • Nuclear Proteins
  • RNA, Messenger
  • Smarca2 protein, mouse
  • TATA-Box Binding Protein
  • Transcription Factor TFIIB
  • Transcription Factors
  • Smarca4 protein, mouse
  • DNA Helicases