Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells.
Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells.
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DOI：
10.1016/j.molcel.2011.04.005
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发表时间：
2011-05-20
期刊：
影响因子：
16
通讯作者：
Shi YG
中科院分区：
文献类型：
--
作者：
Xu Y;Wu F;Tan L;Kong L;Xiong L;Deng J;Barbera AJ;Zheng L;Zhang H;Huang S;Min J;Nicholson T;Chen T;Xu G;Shi Y;Zhang K;Shi YG
哺乳动物基因组中胞嘧啶5位（5mC）的DNA甲基化是一个关键的表观遗传事件，对各种细胞过程至关重要。10 - 11易位（Tet） 5mC-羟化酶家族将5mC转化为5-羟甲基胞嘧啶（5hmC），为DNA甲基化的动态调控提供了一种途径。在这里，我们报道Tet1通过其CXXC结构域结合未修饰的C， 5mC-或5hmc -修饰的富含cpg的DNA。Tet1和5hmC的全基因组定位揭示了Tet1控制小鼠胚胎干细胞（mESCs）中5hmC和5mC水平的机制。我们还发现了受Tet1影响的一个全面的基因网络。总的来说，我们的数据表明Tet1通过结合富含cpg的区域来防止不必要的DNA甲基转移酶活性，并通过羟化酶活性将5mC转化为5hmC来控制DNA甲基化。这种Tet1介导的CpG甲基化拮抗作用赋予了Tet1靶点DNA甲基化状态的差异性维持，最终促进了mESC分化和胚胎发育的开始。
DNA methylation at the 5-position of cytosine (5mC) in the mammalian genome is a key epigenetic event critical for various cellular processes. The Ten-eleven translocation (Tet) family of 5mC-hydroxylases, which convert 5mC to 5-hydroxymethylcytosine (5hmC), offers a way for dynamic regulation of DNA methylation. Here we report that Tet1 binds unmodified C, 5mC- or 5hmC-modified CpG-rich DNA through its CXXC domain. Genome-wide mapping of Tet1 and 5hmC reveals mechanisms by which Tet1 controls 5hmC and 5mC levels in mouse embryonic stem cells (mESCs). We also uncover a comprehensive gene network influenced by Tet1. Collectively, our data suggest that Tet1 controls DNA methylation both by binding to CpG-rich regions to prevent unwanted DNA methyltransferase activity, and by converting 5mC to 5hmC through hydroxylase activity. This Tet1-mediated antagonism of CpG methylation imparts differential maintenance of DNA methylation status at Tet1 targets, ultimately contributing to mESC differentiation and the onset of embryonic development.
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影响因子：
46.9
作者：
Trapnell C;Williams BA;Pertea G;Mortazavi A;Kwan G;van Baren MJ;Salzberg SL;Wold BJ;Pachter L
通讯作者：
Pachter L
影响因子：
21.3
作者：
Ng, Ray Kit;Dean, Wendy;Dawson, Claire;Lucifero, Diana;Madeja, Zofia;Reik, Wolf;Hemberger, Myriam
通讯作者：
Hemberger, Myriam
影响因子：
46.9
作者：
Deng, Jie;Shoemaker, Robert;Xie, Bin;Gore, Athurva;LeProust, Emily M.;Antosiewicz-Bourget, Jessica;Egli, Dieter;Maherali, Nimet;Park, In-Hyun;Yu, Junying;Daley, George Q.;Eggan, Kevin;Hochedlinger, Konrad;Thomson, James;Wang, Wei;Gao, Yuan;Zhang, Kun
通讯作者：
Zhang, Kun
影响因子：
3.7
作者：
Globisch D;Münzel M;Müller M;Michalakis S;Wagner M;Koch S;Brückl T;Biel M;Carell T
通讯作者：
Carell T
影响因子：
16.8
作者：
Tilgner, Hagen;Nikolaou, Christoforos;Guigo, Roderic
通讯作者：
Guigo, Roderic