H3K4/H3K9me3 Bivalent Chromatin Domains Targeted by Lineage-Specific DNA Methylation Pauses Adipocyte Differentiation

被引：174

作者：

Matsumura, Yoshihiro ^{[1
,4
]}

Nakaki, Ryo ^{[2
]}

Inagaki, Takeshi ^{[1
,4
]}

Yoshida, Ayano ^{[1
,5
]}

Kano, Yuka ^{[1
]}

Kimura, Hiroshi ^{[6
]}

Tanaka, Toshiya ^{[1
,3
,4
]}

Tsutsumi, Shuichi ^{[2
]}

Nakao, Mitsuyoshi ^{[7
]}

Doi, Takefumi ^{[8
]}

Fukami, Kiyoko ^{[5
]}

Osborne, Timothy F. ^{[9
]}

Kodama, Tatsuhiko ^{[3
]}

Aburatani, Hiroyuki ^{[2
,4
]}

Sakai, Juro ^{[1
,4
]}

机构：

[1] Univ Tokyo, Div Metab Med, Meguro Ku, Tokyo 1538904, Japan

[2] Univ Tokyo, Genome Sci Div, Meguro Ku, Tokyo 1538904, Japan

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

[4] Univ Tokyo, TSBMI, Ctr Dis Biol & Integrat Med, Fac Med, Tokyo 1138655, Japan

[5] Tokyo Univ Pharm & Life Sci, Lab Genome & Biosignals, Tokyo 1920392, Japan

[6] Tokyo Inst Technol, Dept Biol Sci, Grad Sch Biosci & Biotechnol, Yokohama, Kanagawa 2268501, Japan

[7] Kumamoto Univ, Dept Med Cell Biol, Inst Mol Embryol & Genet, Kumamoto 8600811, Japan

[8] Osaka Univ, Grad Sch Pharmaceut Sci, Suita, Osaka 5650871, Japan

[9] Sanford Burnham Med Res Inst, Metabol Dis Program, Orlando, FL 32827 USA

来源：

MOLECULAR CELL | 2015年 / 60卷 / 04期

关键词：

EMBRYONIC STEM-CELLS; CPG-BINDING DOMAIN; HISTONE MODIFICATIONS; GENE; TRANSCRIPTION; PROTEIN; LYSINE-9; SETDB1; PHOSPHORYLATION; HETEROCHROMATIN;

D O I：

10.1016/j.molcel.2015.10.025

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：

Bivalent H3K4me3 and H3K27me3 chromatin domains in embryonic stem cells keep active developmental regulatory genes expressed at very low levels and poised for activation. Here, we show an alternative and previously unknown bivalent modified histone signature in lineage-committed mesenchymal stem cells and preadipocytes that pairs H3K4me3 with H3K9me3 to maintain adipogenic master regulatory genes (Cebpa and Pparg) expressed at low levels yet poised for activation when differentiation is required. We show lineage-specific gene-body DNA methylation recruits H3K9 methyltransferase SETDB1, which methylates H3K9 immediately downstream of transcription start sites marked with H3K4me3 to establish the bivalent domain. At the Cebpa locus, this prevents transcription factor C/EBPb binding, histone acetylation, and further H3K4me3 deposition and is associated with pausing of RNA polymerase II, which limits Cebpa gene expression and adipogenesis.

引用

页码：584 / 596

页数：13

共 53 条

[1] JMJD1A is a signal-sensing scaffold that regulates acute chromatin dynamics via SWI/SNF association for thermogenesis [J].