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

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 sh...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2009-04, Vol.106 (14), p.5819-5824
Main Authors: Okamura, Masashi, Kudo, Hiromi, Wakabayashi, Ken-ichi, Tanaka, Toshiya, Nonaka, Aya, Uchida, Aoi, Tsutsumi, Shuichi, Sakakibara, Iori, Naito, Makoto, Osborne, Timothy F, Hamakubo, Takao, Ito, Sadayoshi, Aburatani, Hiroyuki, Yanagisawa, Masashi, Kodama, Tatsuhiko, Sakai, Juro
Format: Article
Language:English
Subjects:
Acetylation
Adipogenesis - genetics
Animals
beta Catenin - metabolism
Chromatin
COUP Transcription Factor I - genetics
COUP Transcription Factor I - physiology
DNA-Binding Proteins - metabolism
Gene Expression Regulation - physiology
Mice
Nuclear Receptor Co-Repressor 2
PPAR gamma - genetics
Rats
Repressor Proteins - metabolism
RNA, Messenger - genetics
Signal Transduction - physiology
Wnt Proteins - metabolism
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Summary: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.
ISSN:1091-6490
DOI:10.1073/pnas.0901676106