@article{79f13e6a0c68424d8aef21a0be220dc1,
title = "Distinct epigenomic landscapes of pluripotent and lineage-committed human cells",
abstract = "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.",
author = "Hawkins, {R. David} and Hon, {Gary C.} and Lee, {Leonard K.} and Queminh Ngo and Ryan Lister and Mattia Pelizzola and Edsall, {Lee E.} and Samantha Kuan and Ying Luu and Sarit Klugman and Jessica Antosiewicz-Bourget and Zhen Ye and Celso Espinoza and Saurabh Agarwahl and Li Shen and Victor Ruotti and Wei Wang and Ron Stewart and Thomson, {James A.} and Ecker, {Joseph R.} and Bing Ren",
note = "Funding Information: We acknowledge Bradley Bernstein and the ENCODE Chromatin Group at Broad Institute and MGH for generating the H3K27me3 data sets for HUVEC, NHEK, GM, and K562 cell types. These data were used for validation during the revision and were under embargo until October 7, 2009. R.D.H. is supported by an American Cancer Society Postdoctoral Fellowship. R.L. is supported by a Human Frontier Science Program Long-term Fellowship. This work was supported by the following: NIH Epigenomics Roadmap Project (to B.R., J.A.T., J.R.E., and W.W.), the California Institute for Regenerative Medicine (B.R.), the Ludwig Institute for Cancer Research (B.R.), the Mary K. Chapman Foundation (J.R.E.), and the J.T.F. Morgridge Institute for Research (J.A.T.). This study was carried out as part of the NIH Roadmap Epigenomics Program ( http://nihroadmap.nih.gov/epigenomics/referenceepigenomeconsortium.asp ). ",
year = "2010",
month = may,
day = "7",
doi = "10.1016/j.stem.2010.03.018",
language = "English (US)",
volume = "6",
pages = "479--491",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "5",
}