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

  1. Yi Zhang3,4,8
  1. 1Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA;
  2. 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;
  3. 3Howard Hughes Medical Institute, University of North Carolina, Chapel Hill, North Caroline 27599, USA;
  4. 4Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA;
  5. 5Laboratory of Human Environmental Epigenomes, Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21025, USA;
  6. 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.

    Keywords

    Footnotes

    • Received January 25, 2011.
    • Accepted February 22, 2011.
    | Table of Contents

    Life Science Alliance