Genome-wide analysis of 5-hydroxymethylcytosine distribution reveals its dual function in transcriptional regulation in mouse embryonic stem cells

Hao Wu; Ana C. D'Alessio; Shinsuke Ito; Zhibin Wang; Kairong Cui; Keji Zhao; Yi Eve Sun; Yi Zhang

doi:10.1101/gad.2036011

Genome-wide analysis of 5-hydroxymethylcytosine distribution reveals its dual function in transcriptional regulation in mouse embryonic stem cells

¹Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA;
²Department of Psychiatry and Biobehavioral Sciences, Intellectual Development and Disabilities Research Center, Semel Institute of Neuroscience and Human Behavior, University of California at Los Angeles, Los Angeles, California 90095, USA;
³Howard Hughes Medical Institute, University of North Carolina, Chapel Hill, North Caroline 27599, USA;
⁴Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA;
⁵Laboratory of Human Environmental Epigenomes, Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21025, USA;
⁶Laboratory of Molecular Immunology, The National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA

↵7 Present address: Cardiovascular Research Center, Massachusetts General Hospital, 185 Cambridge St., Boston, MA 02114, USA, and Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Ave., Cambridge, MA 02138, USA.

Abstract

Recent studies have demonstrated that the Ten-eleven translocation (Tet) family proteins can enzymatically convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). While 5mC has been studied extensively, little is known about the distribution and function of 5hmC. Here we present a genome-wide profile of 5hmC in mouse embryonic stem (ES) cells. A combined analysis of global 5hmC distribution and gene expression profile in wild-type and Tet1-depleted ES cells suggests that 5hmC is enriched at both gene bodies of actively transcribed genes and extended promoter regions of Polycomb-repressed developmental regulators. Thus, our study reveals the first genome-wide 5hmC distribution in pluripotent stem cells, and supports its dual function in regulating gene expression.