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

Masashi Okamura, Hiromi Kudo, Ken Ichi Wakabayashi, Toshiya Tanaka, Aya Nonaka, Aoi Uchida, Shuichi Tsutsumi, Iori Sakakibara, Makoto Naito, Timothy Osborne, Takao Hamakubo, Sadayoshi Ito, Hiroyuki Aburatani, Masashi Yanagisawa, Tatsuhiko Kodama, Juro Sakai

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5819-5824
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number14
DOIs
StatePublished - Apr 7 2009
Externally publishedYes

Fingerprint

Catenins
Adipogenesis
Peroxisome Proliferator-Activated Receptors
Gene Expression
Nuclear Receptor Co-Repressor 2
Chromatin Immunoprecipitation
Introns
Chromatin
Exons
Messenger RNA

Keywords

  • ChIP-chip
  • Epigenome
  • Histone modification
  • Obesity
  • Wnt

ASJC Scopus subject areas

  • General

Cite this

COUP-TFII acts downstream of Wnt/β-catenin signal to silence PPARγ gene expression and repress adipogenesis. / Okamura, Masashi; Kudo, Hiromi; Wakabayashi, Ken Ichi; Tanaka, Toshiya; Nonaka, Aya; Uchida, Aoi; Tsutsumi, Shuichi; Sakakibara, Iori; Naito, Makoto; Osborne, Timothy; Hamakubo, Takao; Ito, Sadayoshi; Aburatani, Hiroyuki; Yanagisawa, Masashi; Kodama, Tatsuhiko; Sakai, Juro.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 14, 07.04.2009, p. 5819-5824.

Research output: Contribution to journalArticle

Okamura, M, Kudo, H, Wakabayashi, KI, Tanaka, T, Nonaka, A, Uchida, A, Tsutsumi, S, Sakakibara, I, Naito, M, Osborne, T, Hamakubo, T, Ito, S, Aburatani, H, Yanagisawa, M, Kodama, T & Sakai, J 2009, 'COUP-TFII acts downstream of Wnt/β-catenin signal to silence PPARγ gene expression and repress adipogenesis', Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 14, pp. 5819-5824. https://doi.org/10.1073/pnas.0901676106
Okamura, Masashi ; Kudo, Hiromi ; Wakabayashi, Ken Ichi ; Tanaka, Toshiya ; Nonaka, Aya ; Uchida, Aoi ; Tsutsumi, Shuichi ; Sakakibara, Iori ; Naito, Makoto ; Osborne, Timothy ; Hamakubo, Takao ; Ito, Sadayoshi ; Aburatani, Hiroyuki ; Yanagisawa, Masashi ; Kodama, Tatsuhiko ; Sakai, Juro. / COUP-TFII acts downstream of Wnt/β-catenin signal to silence PPARγ gene expression and repress adipogenesis. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 14. pp. 5819-5824.
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AU - Tsutsumi, Shuichi

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