@article{bbb48706f4a044749b74db34cfb8db76,
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.",
author = "Wei Xie and Schultz, {Matthew D.} and Ryan Lister and Zhonggang Hou and Nisha Rajagopal and Pradipta Ray and Whitaker, {John W.} and Shulan Tian and Hawkins, {R. David} and Danny Leung and Hongbo Yang and Tao Wang and Lee, {Ah Young} and Swanson, {Scott A.} and Jiuchun Zhang and Yun Zhu and Audrey Kim and Nery, {Joseph R.} and Urich, {Mark A.} and Samantha Kuan and Yen, {Chia An} and Sarit Klugman and Pengzhi Yu and Kran Suknuntha and Propson, {Nicholas E.} and Huaming Chen and Edsall, {Lee E.} and Ulrich Wagner and Yan Li and Zhen Ye and Ashwinikumar Kulkarni and Zhenyu Xuan and Chung, {Wen Yu} and Chi, {Neil C.} and Antosiewicz-Bourget, {Jessica E.} and Igor Slukvin and Ron Stewart and Zhang, {Michael Q.} and Wei Wang and Thomson, {James A.} and Ecker, {Joseph R.} and Bing Ren",
note = "Funding Information: This work is supported by the NIH Epigenome Roadmap Project (U01 ES017166) and also in part by NSFC 91019016 and NIH R01 HG001696 (M.Q.Z.), NIH P01 GM081629 (J.A.T.), and CIRM RN2-00905-1 (B.R.). J.R.E. is a Howard Hughes Medical Institute and Gordon and Betty Moore Investigator. N.C.C. is funded by grants from the NIH/NHLBI. H.Y. is funded by grants from the American Heart Association (12POST12050080). We thank Drs. Tomek Swigut and Joanna Wysocka for sharing the zebrafish enhancer reporter vector. We thank Dr. John Stamatoyannopoulos for generating and providing access to the DNase-seq data sets. We also thank members of the Ren lab for helpful comments of the manuscript. B.R., J.A.T., J.R.E., W.W., and M.Q.Z. designed and supervised the research. Z.H., J.Z., P.Y., N.E.P., K.S., J.E.A.-B., and I.S. performed/supervised the H1 differentiation experiments. W.X., R.D.H., D.L., A.Y.L., A.K., S. Kuan, C.Y., and S. Klugman performed ChIP-seq experiments. R.L. and J.R.N. performed MethylC-seq experiments. M.A.U., Y.L., and Y.Z. performed RNA-seq experiments. H.Y. and N.C.C. performed/supervised the enhancer-reporter assay in zebrafish. W.X., M.D.S., N.R., P.R., J.W.W., S.T., T.W., S.A.S., Y.Z., R.L., H.C., L.E.E., U.W., A.K., Z.X., W.Y.C., and R.S. analyzed data. W.X., B.R., and R.S. prepared the manuscript. B.R., J.A.T., J.R.E., W.W., and M.Q.Z. are equally responsible for the analysis results. M.D.S., R.L., Z.H., N.R., P.R., J.W.W., S.T., R.D.H., and D.L. contributed equally to this work. ",
year = "2013",
month = may,
day = "23",
doi = "10.1016/j.cell.2013.04.022",
language = "English (US)",
volume = "153",
pages = "1134--1148",
journal = "Cell",
issn = "0092-8674",
publisher = "Elsevier B.V.",
number = "5",
}