期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：14
页码：5819-5824
DOI：10.1073/pnas.0901676106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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 PPAR{gamma}1 and {gamma}2 mRNAs. This maintains the local chromatin in a hypoacetylated state and represses PPAR{gamma} 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 PPAR{gamma} gene expression and the inhibition of adipogenesis.
