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

被引：169

作者：

Okamura, Masashi ^{[1
,2
]}

Kudo, Hiromi ^{[1
]}

Wakabayashi, Ken-ichi ^{[1
,3
]}

Tanaka, Toshiya ^{[1
]}

Nonaka, Aya ^{[1
,3
]}

Uchida, Aoi ^{[1
]}

Tsutsumi, Shuichi ^{[1
,3
]}

Sakakibara, Iori ^{[1
]}

Naito, Makoto ^{[4
]}

Osborne, Timothy F. ^{[5
]}

Hamakubo, Takao ^{[1
]}

Ito, Sadayoshi ^{[2
]}

Aburatani, Hiroyuki ^{[1
,3
]}

Yanagisawa, Masashi ^{[6
,7
]}

Kodama, Tatsuhiko ^{[1
,8
]}

Sakai, Juro ^{[1
,8
]}

机构：

[1] Univ Tokyo, Lab Syst Biol & Med, Res Ctr Adv Sci & Technol, Meguro Ku, Tokyo 1538904, Japan

[2] Tohoku Univ, Grad Sch Med, Dept Med, Div Nephrol Endocrinol & Vasc Med, Sendai, Miyagi 9808574, Japan

[3] Univ Tokyo, Res Ctr Adv Sci & Technol, Genome Sci Div, Meguro Ku, Tokyo 1538904, Japan

[4] Niigata Univ, Grad Sch Med & Dent Sci, Div Cellular & Mol Pathol, Dept Cellular Funct, Niigata 9518510, Japan

[5] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92717 USA

[6] Univ Texas SW Med Ctr Dallas, Dept Mol Genet, Dallas, TX 75390 USA

[7] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA

[8] Univ Tokyo, Translat Syst Biol & Med Initiat, Tokyo 1538904, Japan

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2009年 / 106卷 / 14期

关键词：

ChIP-chip; epigenome; histone modification; obesity; Wnt; ADIPOCYTE DIFFERENTIATION; HISTONE MODIFICATION; COLON-CARCINOMA; C-MYC; RECEPTOR; TRANSCRIPTION; INHIBITION; ACTIVATION; REGULATOR;

D O I：

10.1073/pnas.0901676106

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

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.

引用

页码：5819 / 5824

页数：6

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