Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells.
Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells.
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DOI：
10.1038/nature09934
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发表时间：
2011-05-19
期刊：
影响因子：
64.8
通讯作者：
Zhang, Yi
中科院分区：
文献类型：
--
作者：
Wu, Hao;D'Alessio, Ana C.;Ito, Shinsuke;Xia, Kai;Wang, Zhibin;Cui, Kairong;Zhao, Keji;Sun, Yi Eve;Zhang, Yi
通过DNA甲基化（5-甲基胞嘧啶）对哺乳动物基因组的表观遗传修饰对染色质结构、基因表达和细胞身份的维持具有深远影响。最近的证据表明，10 - 11易位（泰特）蛋白家族的成员可以将5-甲基胞嘧啶转化为5-羟甲基胞嘧啶提出的可能性，泰特蛋白能够建立一个独特的表观遗传状态。我们最近证明Tet 1在小鼠胚胎干细胞（ES）中特异性表达，并且是ES细胞维持所需的。使用染色质免疫沉淀结合高通量DNA测序，在这里，我们表明在小鼠ES细胞中，Tet 1优先结合到CpG丰富的序列在启动子的转录活性和Polycomb抑制基因。尽管在许多Tet 1结合位点的DNA甲基化水平增加，Tet 1耗竭不会导致所有Tet 1靶点的下调。有趣的是，虽然Tet 1介导的启动子低甲基化是维持一组转录活性基因表达所必需的，但它也参与了Polycomb靶向发育调节因子的抑制。Tet 1通过促进PRC 2向富含CpG的基因启动子的募集来沉默这组基因。因此，我们的研究不仅确定了Tet 1在调节富含CpG的启动子的DNA甲基化水平中的作用，而且还揭示了Tet 1在促进多能性因子转录以及参与Polycomb靶向发育调节因子的抑制中的双重功能。
Epigenetic modification of the mammalian genome by DNA methylation (5-methylcytosine) has a profound impact on chromatin structure, gene expression and maintenance of cellular identity. The recent demonstration that members of the Ten-eleven translocation (Tet) family of proteins can convert 5-methylcytosine to 5-hydroxymethylcytosine raised the possibility that Tet proteins are capable of establishing a distinct epigenetic state. We have recently demonstrated that Tet1 is specifically expressed in murine embryonic stem (ES) cells and is required for ES cell maintenance. Using chromatin immunoprecipitation coupled with high-throughput DNA sequencing, here we show in mouse ES cells that Tet1 is preferentially bound to CpG-rich sequences at promoters of both transcriptionally active and Polycomb-repressed genes. Despite an increase in levels of DNA methylation at many Tet1-binding sites, Tet1 depletion does not lead to downregulation of all the Tet1 targets. Interestingly, although Tet1-mediated promoter hypomethylation is required for maintaining the expression of a group of transcriptionally active genes, it is also involved in repression of Polycomb-targeted developmental regulators. Tet1 contributes to silencing of this group of genes by facilitating recruitment of PRC2 to CpG-rich gene promoters. Thus, our study not only establishes a role for Tet1 in modulating DNA methylation levels at CpG-rich promoters, but also reveals a dual function of Tet1 in promoting transcription of pluripotency factors as well as participating in the repression of Polycomb-targeted developmental regulators.
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DOI：
10.1126/science.1190485
发表时间：
2010-07-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Wu H;Coskun V;Tao J;Xie W;Ge W;Yoshikawa K;Li E;Zhang Y;Sun YE
通讯作者：
Sun YE
影响因子：
16
作者：
Blackledge NP;Zhou JC;Tolstorukov MY;Farcas AM;Park PJ;Klose RJ
通讯作者：
Klose RJ
DOI：
10.1126/science.1162253
发表时间：
2008-12-19
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Seila AC;Calabrese JM;Levine SS;Yeo GW;Rahl PB;Flynn RA;Young RA;Sharp PA
通讯作者：
Sharp PA
影响因子：
46.9
作者：
Ji, Hongkai;Jiang, Hui;Ma, Wenxiu;Johnson, David S.;Myers, Richard M.;Wong, Wing H.
通讯作者：
Wong, Wing H.
影响因子：
64.8
作者：
Pasini, Diego;Cloos, Paul A. C.;Helin, Kristian
通讯作者：
Helin, Kristian