The Peroxisome Proliferator-Activated Receptor γ/Retinoid X Receptor α Heterodimer Targets the Histone Modification Enzyme PR-Set7/Setd8 Gene and Regulates Adipogenesis through a Positive Feedback Loop

被引：161

作者：

Wakabayashi, Ken-ichi ^{[2
,6
]}

Okamura, Masashi ^{[1
]}

Tsutsumi, Shuichi ^{[2
]}

Nishikawa, Naoko S. ^{[3
]}

Tanaka, Toshiya ^{[1
]}

Sakakibara, Iori ^{[1
]}

Kitakami, Jun-ichi ^{[3
]}

Ihara, Sigeo ^{[3
]}

Hashimoto, Yuichi ^{[6
]}

Hamakubo, Takao ^{[4
]}

Kodama, Tatsuhiko ^{[5
]}

Aburatani, Hiroyuki ^{[2
]}

Sakai, Juro ^{[1
]}

机构：

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

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

[3] Univ Tokyo, Adv Sci & Technol Res Ctr, Lab Syst Biol & Med, Dynam Bioinformat Div,Meguro Ku, Tokyo 1538904, Japan

[4] Univ Tokyo, Adv Sci & Technol Res Ctr, Lab Syst Biol & Med, Membrane Prot Div,Meguro Ku, Tokyo 1538904, Japan

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

[6] Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan

来源：

MOLECULAR AND CELLULAR BIOLOGY | 2009年 / 29卷 / 13期

关键词：

PPAR-GAMMA; TRANSCRIPTIONAL REGULATION; EXPRESSION; BINDING; PROMOTER; DIFFERENTIATION; ORGANIZATION; FIBROBLASTS; METHYLATION; REQUIRES;

D O I：

10.1128/MCB.01856-08

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Control of cell differentiation occurs through transcriptional mechanisms and through epigenetic modification. Using a chromatin immunoprecipitation-on-chip approach, we performed a genome-wide search for target genes of peroxisome proliferator-activated receptor gamma (PPAR gamma) and its partner protein retinoid X receptor alpha during adipogenesis. We show that these two receptors target several genes that encode histone lysine methyltransferase SET domain proteins. The histone H4 Lys 20 (H4K20) monomethyltransferase PR-Set7/Setd8 gene is upregulated by PPAR gamma during adipogenesis, and the knockdown of PR-Set7/Setd8 suppressed adipogenesis. Intriguingly, monomethylated H4K20 (H4K20me1) levels are robustly increased toward the end of differentiation. PR-Set7/Setd8 positively regulates the expression of PPAR gamma and its targets through H4K20 monomethylation. Furthermore, the activation of PPAR gamma transcriptional activity leads to the induction of H4K20me1 modification of PPAR gamma and its targets and thereby promotes adipogenesis. We also show that PPAR gamma targets PPAR gamma 2 and promotes its gene expression through H4K20 monomethylation. Our results connect transcriptional regulation and epigenetic chromatin modulation through H4K20 monomethylation during adipogenesis through a feedback loop.

引用

页码：3544 / 3555

页数：12

共 34 条

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