title: Epigenomic analysis of multilineage differentiation of human embryonic stem cells.
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.
authors.affiliation: Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Schultz
authors.forename: Ryan
authors.initials: R
authors.lastname: Lister
authors.forename: Zhonggang
authors.initials: Z
authors.lastname: Hou
authors.forename: Nisha
authors.initials: N
authors.lastname: Rajagopal
authors.forename: Pradipta
authors.initials: P
authors.lastname: Ray
authors.forename: John W
authors.initials: JW
authors.lastname: Whitaker
authors.forename: Shulan
authors.initials: S
authors.lastname: Tian
authors.forename: R David
authors.initials: RD
authors.lastname: Hawkins
authors.forename: Danny
authors.initials: D
authors.lastname: Leung
authors.forename: Hongbo
authors.initials: H
authors.lastname: Yang
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Ah Young
authors.initials: AY
authors.lastname: Lee
authors.forename: Scott A
authors.initials: SA
authors.lastname: Swanson
authors.forename: Jiuchun
authors.initials: J
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhu
authors.forename: Audrey
authors.initials: A
authors.lastname: Kim
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Nery
authors.forename: Mark A
authors.initials: MA
authors.lastname: Urich
authors.forename: Samantha
authors.initials: S
authors.lastname: Kuan
authors.forename: Chia-an
authors.initials: CA
authors.lastname: Yen
authors.forename: Sarit
authors.initials: S
authors.lastname: Klugman
authors.forename: Pengzhi
authors.initials: P
authors.lastname: Yu
authors.forename: Kran
authors.initials: K
authors.lastname: Suknuntha
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Propson
authors.forename: Huaming
authors.initials: H
authors.lastname: Chen
authors.forename: Lee E
authors.initials: LE
authors.lastname: Edsall
authors.forename: Ulrich
authors.initials: U
authors.lastname: Wagner
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Zhen
authors.initials: Z
authors.lastname: Ye
authors.forename: Ashwinikumar
authors.initials: A
authors.lastname: Kulkarni
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Xuan
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Chung
authors.forename: Neil C
authors.initials: NC
authors.lastname: Chi
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Antosiewicz-Bourget
authors.forename: Igor
authors.initials: I
authors.lastname: Slukvin
authors.forename: Ron
authors.initials: R
authors.lastname: Stewart
authors.forename: Michael Q
authors.initials: MQ
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: James A
authors.initials: JA
authors.lastname: Thomson
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Ecker
authors.forename: Bing
authors.initials: B
authors.lastname: Ren
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002843:Chromatin / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D057890:Epigenomics; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000378:metabolism; D006801:Humans; D008745:Methylation; D009369:Neoplasms / Q000235:genetics; D011401:Promoter Regions, Genetic; D015027:Zebrafish / Q000196:embryology
chemical_list: D002843:Chromatin; D006657:Histones