Large histone H3 lysine 9 dimethylated chromatin blocks distinguish differentiated from embryonic stem cells

被引：461

作者：

Wen, Bo ^{[1
,2
]}

Wu, Hao ^{[1
,3
]}

Shinkai, Yoichi ^{[4
]}

Irizarry, Rafael A. ^{[1
,3
]}

Feinberg, Andrew P. ^{[1
,2
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

[3] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA

[4] Kyoto Univ, Inst Virus Res, Sakyo Ku, Kyoto 606, Japan

来源：

NATURE GENETICS | 2009年 / 41卷 / 02期

基金：

美国国家卫生研究院;

关键词：

NUCLEAR-ORGANIZATION; GENOME; CHROMOSOMES; PLASTICITY; MOUSE;

D O I：

10.1038/ng.297

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Higher eukaryotes must adapt a totipotent genome to specialized cell types with stable but limited functions. One potential mechanism for lineage restriction is changes in chromatin, and differentiation-related chromatin changes have been observed for individual genes(1,2). We have taken a genome-wide view of histone H3 lysine 9 dimethylation (H3K9Me2) and find that differentiated tissues show surprisingly large K9-modified regions (up to 4.9 Mb). These regions are highly conserved between human and mouse and are differentiation specific, covering only similar to 4% of the genome in undifferentiated mouse embryonic stem (ES) cells, compared to 31% in differentiated ES cells, similar to 46% in liver and similar to 10% in brain. These modifications require histone methyltransferase G9a and are inversely related to expression of genes within the regions. We term these regions large organized chromatin K9 modifications (LOCKs). LOCKs are substantially lost in cancer cell lines, and they may provide a cell type-heritable mechanism for phenotypic plasticity in development and disease.

引用

页码：246 / 250

页数：5

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