Epigenomic Analysis of Multilineage Differentiation of Human Embryonic Stem Cells.

Publication Year: 
Wei Xie
Matthew D Schultz
Ryan Lister
Zhonggang Hou
Nisha Rajagopal
Pradipta Ray
John W Whitaker
Shulan Tian
R David Hawkins
Danny Leung
Hongbo Yang
Tao Wang
Ah Young Lee
Scott A Swanson
Jiuchun Zhang
Yun Zhu
Audrey Kim
Joseph R Nery
Mark A Urich
Samantha Kuan
Chia-An Yen
Sarit Klugman
Pengzhi Yu
Kran Suknuntha
Nicholas E Propson
Huaming Chen
Lee E Edsall
Ulrich Wagner
Yan Li
Zhen Ye
Ashwinikumar Kulkarni
Zhenyu Xuan
Wen-Yu Chung
Neil C Chi
Jessica E Antosiewicz-Bourget
Igor Slukvin
Ron Stewart
Michael Q Zhang
Wei Wang
James A Thomson
Joseph R Ecker
Bing Ren
PubMed link: 
Public Summary: 
Scientific Abstract: 
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.