Sequential gene promoter interactions of C/EBPbeta, C/EBPalpha, and PPARgamma during adipogenesis

Biochem Biophys Res Commun. 2004 Jun 18;319(1):235-9. doi: 10.1016/j.bbrc.2004.04.176.


Treatment of 3T3-L1 preadipocytes with differentiation inducers triggers a cascade in which C/EBPbeta is rapidly expressed, followed by C/EBPalpha and PPARgamma. C/EBPalpha and PPARgamma then activate the expression of adipocyte genes that produce the differentiated phenotype. Circumstantial evidence indicates that C/EBPbeta activates transcription of the C/EBPalpha and PPARgamma genes, both of which possess C/EBP regulatory elements in their proximal promoters. Although C/EBPbeta is expressed immediately upon induction of differentiation, acquisition of DNA binding activity is delayed for approximately 14h. Chromatin immunoprecipitation (ChIP) analysis conducted 24h after induction revealed that C/EBPbeta binds to C/EBP regulatory elements in the proximal promoters of the C/EBPalpha and PPARgamma genes. After an additional delay ChIP analysis showed that C/EBPalpha binds to its own promoter and to the promoters of the PPARgamma and 422/aP2 genes. These findings support the view that once expressed, C/EBPalpha is responsible for maintaining the expression of PPARgamma and C/EBPalpha, as well as adipocyte proteins (e.g., 422/aP2) in the terminally differentiated state. Together these findings provide compelling evidence that C/EBPbeta, C/EBPalpha, and PPARgamma participate in a cascade during adipogenesis.

Publication types

  • Duplicate Publication
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / metabolism
  • Adipose Tissue / metabolism*
  • Animals
  • CCAAT-Enhancer-Binding Protein-alpha / genetics*
  • CCAAT-Enhancer-Binding Protein-beta / genetics*
  • Cell Differentiation
  • Chromatin / chemistry
  • Chromatin / metabolism
  • DNA / chemistry
  • Immunoblotting
  • Mice
  • Phenotype
  • Precipitin Tests
  • Promoter Regions, Genetic*
  • Protein Binding
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Time Factors
  • Transcription Factors / genetics*
  • Transcription, Genetic


  • CCAAT-Enhancer-Binding Protein-alpha
  • CCAAT-Enhancer-Binding Protein-beta
  • Chromatin
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • DNA