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

Genome-wide analysis of 5-hydroxymethylcytosine distribution reveals its dual function in transcriptional regulation in mouse embryonic stem cells
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DOI:
10.1101/gad.2036011
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发表时间:
2011-04-01
影响因子:
10.5
通讯作者:
Zhang, Yi
Zhang, Yi
中科院分区:
生物学1区
文献类型:
--
作者:
Wu, Hao;D'Alessio, Ana C.;Zhang, Yi

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最近的研究表明,十-十一易位(泰特)家族蛋白可以酶促将5-甲基胞嘧啶(5 mC)转化为5-羟甲基胞嘧啶(5 hmC)。虽然5 mC已被广泛研究,但对5 hmC的分布和功能知之甚少。在这里,我们提出了一个全基因组的5 hmC在小鼠胚胎干细胞(ES)的配置文件。全球5 hmC分布和基因表达谱在野生型和Tet 1耗尽ES细胞的综合分析表明,5 hmC是丰富的两个基因体的积极转录的基因和扩展的启动子区的Polycomb抑制发育调节。因此,我们的研究揭示了多能干细胞中第一个全基因组5 hmC分布,并支持其在调节基因表达方面的双重功能。
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.