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

Wnt signaling through b-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...

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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:
adipogenesis
catenin
Chromatin
DNA microarrays
Exons
Gene expression
Introns
Peroxisome proliferator-activated receptors
Preadipocytes
Signal transduction
SMRT protein
Tcf protein
Wnt protein
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Summary:Wnt signaling through b-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/b-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 PPARg1 and g2 mRNAs. This maintains the local chromatin in a hypoacetylated state and represses PPARg 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/b-catenin signaling to repression of PPARg gene expression and the inhibition of adipogenesis.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0901676106