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

被引:434
作者
Wu, Hao [2 ,3 ]
D'Alessio, Ana C. [1 ,4 ]
Ito, Shinsuke [1 ,4 ]
Wang, Zhibin [5 ]
Cui, Kairong [6 ]
Zhao, Keji [6 ]
Sun, Yi Eve [2 ,3 ]
Zhang, Yi [1 ,4 ]
机构
[1] Univ N Carolina, Howard Hughes Med Inst, Chapel Hill, NC 27599 USA
[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Intellectual Dev & Disabil Res Ctr, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA
[4] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA
[5] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Lab Human Environm Epigenomes, Baltimore, MD 21025 USA
[6] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA
关键词
Tet1; 5-methylcytosine (5mC); 5-hydroxymethylcytosine (5hmC); mouse embryonic stem cells; genome-wide 5hmC distribution; Polycomb repression; DNA METHYLATION; PLURIPOTENT; CONVERSION; MAPS;
D O I
10.1101/gad.2036011
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:679 / 684
页数:6
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