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

M Okamura, H Kudo, K Wakabayashi… - Proceedings of the …, 2009 - National Acad Sciences
M Okamura, H Kudo, K Wakabayashi, T Tanaka, A Nonaka, A Uchida, S Tsutsumi…
Proceedings of the National Academy of Sciences, 2009National Acad Sciences
Wnt signaling through β-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/β-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 PPARγ1 and γ2 mRNAs. This maintains the …
Wnt signaling through β-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/β-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 PPARγ1 and γ2 mRNAs. This maintains the local chromatin in a hypoacetylated state and represses PPARγ 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/β-catenin signaling to repression of PPARγ gene expression and the inhibition of adipogenesis.
National Acad Sciences