COUP-TFII acts downstream of Wnt/beta-catenin signal to silence PPARgamma gene expression and repress adipogenesis

Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5819-24. doi: 10.1073/pnas.0901676106. Epub 2009 Mar 23.


Wnt signaling through beta-catenin and TCF maintains preadipocytes in an un-differentiated proliferative state; however, the molecular pathway has not been completely defined. By integrating gene expression microarray, chromatin immunoprecipitation-chip, and cell-based experimental approaches, we show that Wnt/beta-catenin signaling activates the expression of COUP-TFII which recruits the SMRT corepressor complex to the first introns located downstream from the first exons of both PPARgamma1 and gamma2 mRNAs. This maintains the local chromatin in a hypoacetylated state and represses PPARgamma gene expression to inhibit adipogenesis. Our experiments define the COUP-TFII/SMRT complex as a previously unappreciated component of the linear pathway that directly links Wnt/beta-catenin signaling to repression of PPARgamma gene expression and the inhibition of adipogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Adipogenesis / genetics*
  • Animals
  • COUP Transcription Factor I / genetics
  • COUP Transcription Factor I / physiology*
  • Chromatin
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation / physiology*
  • Mice
  • Nuclear Receptor Co-Repressor 2
  • PPAR gamma / genetics*
  • RNA, Messenger / genetics
  • Rats
  • Repressor Proteins / metabolism*
  • Signal Transduction / physiology*
  • Wnt Proteins / metabolism*
  • beta Catenin / metabolism*


  • COUP Transcription Factor I
  • Chromatin
  • DNA-Binding Proteins
  • Ncor2 protein, mouse
  • Ncor2 protein, rat
  • Nuclear Receptor Co-Repressor 2
  • PPAR gamma
  • RNA, Messenger
  • Repressor Proteins
  • Wnt Proteins
  • beta Catenin