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

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

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Laboratory of Systems Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1, Komaba, Meguro-ku, Tokyo 153-8904, Japan.


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.

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