Epigenomic Analysis of Multilineage Differentiation of Human Embryonic Stem Cells

被引：585

作者：

Xie, Wei ^{[1
]}

Schultz, Matthew D. ^{[2
]}

Lister, Ryan ^{[2
]}

Hou, Zhonggang ^{[3
]}

Rajagopal, Nisha ^{[1
]}

Ray, Pradipta ^{[12
]}

Whitaker, John W. ^{[4
]}

Tian, Shulan ^{[3
]}

Hawkins, R. David ^{[1
]}

Leung, Danny ^{[1
]}

Yang, Hongbo ^{[8
]}

Wang, Tao ^{[4
]}

Lee, Ah Young ^{[1
]}

Swanson, Scott A. ^{[3
]}

Zhang, Jiuchun ^{[3
,9
]}

Zhu, Yun ^{[4
]}

Kim, Audrey ^{[1
]}

Nery, Joseph R. ^{[2
]}

Urich, Mark A. ^{[2
]}

Kuan, Samantha ^{[1
]}

Yen, Chia-an ^{[1
]}

Klugman, Sarit ^{[1
]}

Yu, Pengzhi ^{[3
]}

Suknuntha, Kran ^{[13
]}

Propson, Nicholas E. ^{[3
]}

Chen, Huaming ^{[2
]}

Edsall, Lee E. ^{[1
]}

Wagner, Ulrich ^{[1
]}

Li, Yan ^{[1
]}

Ye, Zhen ^{[1
]}

Kulkarni, Ashwinikumar ^{[12
]}

Xuan, Zhenyu ^{[12
]}

Chung, Wen-Yu ^{[12
]}

Chi, Neil C. ^{[8
]}

Antosiewicz-Bourget, Jessica E. ^{[3
]}

Slukvin, Igor ^{[9
,10
,13
]}

Stewart, Ron ^{[3
]}

Zhang, Michael Q. ^{[12
,14
]}

Wang, Wei ^{[4
,7
]}

Thomson, James A. ^{[3
,10
,11
]}

Ecker, Joseph R. ^{[2
]}

Ren, Bing ^{[1
,5
,6
]}

机构：

[1] Ludwig Inst Canc Res, La Jolla, CA 92093 USA

[2] Salk Inst Biol Studies, Howard Hughes Med Inst, Genom Anal Lab, La Jolla, CA 92037 USA

[3] Morgridge Inst Res, Madison, WI 53707 USA

[4] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA

[5] Univ Calif San Diego, Inst Genom Med, Dept Cellular & Mol Med, La Jolla, CA 92093 USA

[6] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA

[7] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA

[8] Univ Calif San Diego, Dept Med, Div Cardiol, La Jolla, CA 92093 USA

[9] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA

[10] Univ Wisconsin, Dept Cell & Regenerat Biol, Madison, WI 53715 USA

[11] Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA

[12] Univ Texas Dallas, Ctr Syst Biol, Dept Mol & Cell Biol, Richardson, TX 75080 USA

[13] Univ Wisconsin, Sch Med, Dept Pathol & Lab Med, Madison, WI 53792 USA

[14] Tsinghua Univ, Tsinghua Natl Lab Informat Sci & Technol, Ctr Synthet & Syst Biol, Bioinformat Div, Beijing 100084, Peoples R China

来源：

CELL | 2013年 / 153卷 / 05期

关键词：

DNA METHYLATION; DEVELOPMENTAL REGULATORS; GENOME; CHROMATIN; MOUSE; PLURIPOTENT; POLYCOMB; STATE; GENES; METHYLOME;

D O I：

10.1016/j.cell.2013.04.022

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：

Epigenetic mechanisms have been proposed to play crucial roles in mammalian development, but their precise functions are only partially understood. To investigate epigenetic regulation of embryonic development, we differentiated human embryonic stem cells into mesendoderm, neural progenitor cells, trophoblast-like cells, and mesenchymal stem cells and systematically characterized DNA methylation, chromatin modifications, and the transcriptome in each lineage. We found that promoters that are active in early developmental stages tend to be CG rich and mainly engage H3K27me3 upon silencing in nonexpressing lineages. By contrast, promoters for genes expressed preferentially at later stages are often CG poor and primarily employ DNA methylation upon repression. Interestingly, the early developmental regulatory genes are often located in large genomic domains that are generally devoid of DNA methylation in most lineages, which we termed DNA methylation valleys (DMVs). Our results suggest that distinct epigenetic mechanisms regulate early and late stages of ES cell differentiation.

引用

页码：1134 / 1148

页数：15

共 57 条

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