Differential H3K4 methylation identifies developmentally poised hematopoietic genes

被引：113

作者：

Orford, Keith ^{[2
,3
]}

Kharchenko, Peter ^{[1
,4
]}

Lai, Weil ^{[1
]}

Dao, Maria Carlota ^{[2
,3
]}

Worhunsky, David J. ^{[2
,3
]}

Ferro, Adam ^{[2
,3
]}

Janzen, Viktor ^{[2
,3
]}

Park, Peter J. ^{[1
,4
]}

Scadden, David T. ^{[2
,3
]}

机构：

[1] Brigham & Womens Hosp, Harvard Partners Ctr Genet & Genom, Boston, MA 02115 USA

[2] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA

[3] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA

[4] Childrens Hosp, Informat Program, Boston, MA 02115 USA

来源：

DEVELOPMENTAL CELL | 2008年 / 14卷 / 05期

关键词：

D O I：

10.1016/j.devcel.2008.04.002

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Throughout development, cell fate decisions are converted into epigenetic information that determines cellular identity. Covalent histone modifications are heritable epigenetic marks and are hypothesized to play a central role in this process. In this report, we assess the concordance of histone H3 lysine 4 dimethylation (H3K4me2) and trimethylation (H3K4me3) on a genome-wide scale in erythro, development by analyzing pluripotent, multipotent, and unipotent cell types. Although H3K4me2 and H3K4me3 are concordant at most genes, multi-potential hematopoietic cells have a subset of genes that are differentially methylated (H3K4me2+/me3-). These genes are transcriptionally silent, highly enriched in lineage-specific hematopoietic genes, and uniquely susceptible to differentiation-induced H3K4 demethylation. Self-renewing embryonic stem cells, which restrict H3K4 methylation to genes that contain CpG islands (CGIs), lack H3K4me2+/me3- genes' These data reveal distinct epigenetic regulation of CGI and non-CGI genes during development and indicate an interactive relationship between DNA sequence and differential H3K4 methylation in lineage-specific differentiation.

引用

页码：798 / 809

页数：12

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