Integrating 5-Hydroxymethylcytosine into the Epigenomic Landscape of Human Embryonic Stem Cells

• Type of Material: Article
• Authors: Keith E. Szulwach, Emory University; Xuekun Li, Emory University; Yujing Li, Emory University; Chun-Xiao Song, University of Chicago; Ji Woong Han, Emory University; Sangsung Kim, Emory University; Sandeep Namburi, Emory University; Karen Hermetz, Emory University; Julie J. Kim, Emory University; Katie Rudd, Emory University; Young-sup Yoon, Emory University; Bing Ren, Ludwig Institute for Cancer Research; Chuan He, University of Chicago; Peng Jin, Emory University
• Language: English
• Date: 2011-06-23
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2011 Szulwach et al.
• License: Creative Commons Attribution 2.0 Generic
• Final Published Version (URL): http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1002154
• Title of Journal or Parent Work: PLoS Genetics
• ISSN: 1553-7390
• Volume: 7
• Issue: 6
• Start Page: e1002154
• End Page: e1002154
• Grant/Funding Information: PJ is supported by NIH grants (NS051630 and MH076090).; PJ is the recipient of a Beckman Young Investigator Award, Basil O’Connor Scholar Research Award, and Alfred P. Sloan Research Fellow in Neuroscience.; Y-SY is supported by NIH grant RC1GM092035.; Work in the CH laboratory was partially supported by NIH GM071440.; This work is supported, in part, by the Emory Genetics Discovery Fund.
• Research Categories: Biology, Genetics; Biology, Cell

Abstract

Covalent modification of DNA distinguishes cellular identities and is crucial for regulating the pluripotency and differentiation of embryonic stem (ES) cells. The recent demonstration that 5-methylcytosine (5-mC) may be further modified to 5-hydroxymethylcytosine (5-hmC) in ES cells has revealed a novel regulatory paradigm to modulate the epigenetic landscape of pluripotency. To understand the role of 5-hmC in the epigenomic landscape of pluripotent cells, here we profile the genome-wide 5-hmC distribution and correlate it with the genomic profiles of 11 diverse histone modifications and six transcription factors in human ES cells. By integrating genomic 5-hmC signals with maps of histone enrichment, we link particular pluripotency-associated chromatin contexts with 5-hmC. Intriguingly, through additional correlations with defined chromatin signatures at promoter and enhancer subtypes, we show distinct enrichment of 5-hmC at enhancers marked with H3K4me1 and H3K27ac. These results suggest potential role(s) for 5-hmC in the regulation of specific promoters and enhancers. In addition, our results provide a detailed epigenomic map of 5-hmC from which to pursue future functional studies on the diverse regulatory roles associated with 5-hmC.