Distinct Epigenomic Landscapes of Pluripotent and Lineage-Committed Human Cells

被引：626

作者：

Hawkins, R. David ^{[1
]}

Hon, Gary C. ^{[1
]}

Lee, Leonard K. ^{[1
]}

Ngo, QueMinh ^{[1
]}

Lister, Ryan ^{[2
]}

Pelizzola, Mattia ^{[2
]}

Edsall, Lee E. ^{[1
]}

Kuan, Samantha ^{[1
]}

Luu, Ying ^{[1
]}

Klugman, Sarit ^{[1
]}

Antosiewicz-Bourget, Jessica ^{[3
]}

Ye, Zhen ^{[1
]}

Espinoza, Celso ^{[1
]}

Agarwahl, Saurabh ^{[1
]}

Shen, Li ^{[4
]}

Ruotti, Victor ^{[3
,7
]}

Wang, Wei ^{[4
]}

Stewart, Ron ^{[3
,7
]}

Thomson, James A. ^{[3
,7
,8
,9
]}

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, 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] Genome Ctr Wisconsin, Madison, WI 53706 USA

[8] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53706 USA

[9] Univ Wisconsin, Dept Anat, Madison, WI 53715 USA

来源：

CELL STEM CELL | 2010年 / 6卷 / 05期

关键词：

EMBRYONIC STEM-CELLS; H3K9ME2 CHROMATIN DOMAINS; DNA METHYLATION; HISTONE H3; LYSINE-9; METHYLATION; GENE-EXPRESSION; POLYCOMB; GENOME; FIBROBLASTS; SIGNATURES;

D O I：

10.1016/j.stem.2010.03.018

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Human embryonic stem cells (hESCs) share an identical genome with lineage-committed cells, yet possess the remarkable properties of self-renewal and pluripotency. The diverse cellular properties in different cells have been attributed to their distinct epigenomes, but how much epigenomes differ remains unclear. Here, we report that epigenomic landscapes in hESCs and lineage-committed cells are drastically different. By comparing the chromatin-modification profiles and DNA methylomes in hESCs and primary fibroblasts, we find that nearly one-third of the genome differs in chromatin structure. Most changes arise from dramatic redistributions of repressive H3K9me3 and H3K27me3 marks, which form blocks that significantly expand in fibroblasts. A large number of potential regulatory sequences also exhibit a high degree of dynamics in chromatin modifications and DNA methylation. Additionally, we observe novel, context-dependent relationships between DNA methylation and chromatin modifications. Our results provide new insights into epigenetic mechanisms underlying properties of pluripotency and cell fate commitment.

引用

页码：479 / 491

页数：13

共 72 条

[41] Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution [J].