title: COUP-TFII acts downstream of Wnt/beta-catenin signal to silence PPARgamma gene expression and repress adipogenesis.
abstract: 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.
authors.affiliation: 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.
authors.forename: Masashi
authors.initials: M
authors.lastname: Okamura
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kudo
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Wakabayashi
authors.forename: Toshiya
authors.initials: T
authors.lastname: Tanaka
authors.forename: Aya
authors.initials: A
authors.lastname: Nonaka
authors.forename: Aoi
authors.initials: A
authors.lastname: Uchida
authors.forename: Shuichi
authors.initials: S
authors.lastname: Tsutsumi
authors.forename: Iori
authors.initials: I
authors.lastname: Sakakibara
authors.forename: Makoto
authors.initials: M
authors.lastname: Naito
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Osborne
authors.forename: Takao
authors.initials: T
authors.lastname: Hamakubo
authors.forename: Sadayoshi
authors.initials: S
authors.lastname: Ito
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.forename: Masashi
authors.initials: M
authors.lastname: Yanagisawa
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.forename: Juro
authors.initials: J
authors.lastname: Sakai
mesh_terms: D000107:Acetylation; D050156:Adipogenesis / Q000235:genetics*; D000818:Animals; D051838:COUP Transcription Factor I / Q000235:genetics / Q000502:physiology*; D002843:Chromatin; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D051379:Mice; D056985:Nuclear Receptor Co-Repressor 2; D047495:PPAR gamma / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051838:COUP Transcription Factor I; D002843:Chromatin; D004268:DNA-Binding Proteins; C539131:Ncor2 protein, mouse; C539132:Ncor2 protein, rat; D056985:Nuclear Receptor Co-Repressor 2; D047495:PPAR gamma; D012333:RNA, Messenger; D012097:Repressor Proteins; D051153:Wnt Proteins; D051176:beta Catenin