Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification.
Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification.
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DNA 甲基化是最具特征的表观遗传修饰之一。虽然催化 DNA 甲基化的酶已被表征，但负责逆转过程的酶却一直难以捉摸。最近的一项研究表明，人类Tet1蛋白可以催化DNA的5-甲基-C（5mC）转化为5-羟甲基-C（5hmC），这提高了DNA去甲基化可能是Tet1介导的过程的可能性。在这里，我们扩展了这项研究，证明所有三种小鼠 Tet 蛋白也可以催化类似的反应。有趣的是，Tet1 通过维持 ES 细胞中 Nanog 的表达，在小鼠 ES 细胞维持中发挥重要作用。重要的是，Tet1 敲低介导的 Nanog 下调与其启动子甲基化相关，支持 Tet1 在调节 DNA 甲基化状态中的作用。此外，植入前胚胎中Tet1的敲低导致滋养外胚层分化的偏向。因此，我们的研究不仅揭示了 Tet 蛋白的酶活性，而且还证明了 Tet1 在 ES 细胞维持和 ICM 细胞规范中的作用。
DNA methylation is one of the best-characterized epigenetic modifications . While the enzymes that catalyze DNA methylation have been characterized, enzymes responsible for the reversal process have been elusive . A recent study indicates that the human Tet1 protein could catalyze the conversion of 5-methyl-C (5mC) of DNA to 5-hydroxyl-methyl-C (5hmC), raising the possibility that DNA demethylation may be a Tet1-mediated process . Here we extended this study by demonstrating that all three mouse Tet proteins can also catalyze a similar reaction. Interestingly, Tet1 plays an important role in mouse ES cell maintenance through maintaining the expression of Nanog in ES cells. Importantly, Tet1 knockdown-mediated down-regulation of Nanog correlated with its promoter methylation, supporting a role for Tet1 in regulating DNA methylation status. Furthermore, knockdown of Tet1 in preimplantation embryos resulted in a bias towards trophectoderm differentiation. Thus, our studies not only uncover the enzymatic activity of the Tet proteins, but also demonstrate a role for Tet1 in ES cell maintenance and ICM cell specification.
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DOI：
10.1016/s0006-291x(88)80489-3
发表时间：
1988-03-30
影响因子：
3.1
作者：
CANNON, SV;CUMMINGS, A;TEEBOR, GW
通讯作者：
TEEBOR, GW
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1126/science.1170116
发表时间：
2009-05-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Tahiliani M;Koh KP;Shen Y;Pastor WA;Bandukwala H;Brudno Y;Agarwal S;Iyer LM;Liu DR;Aravind L;Rao A
通讯作者：
Rao A
影响因子：
64.8
作者：
Chambers, Ian;Silva, Jose;Smith, Austin
通讯作者：
Smith, Austin
影响因子：
5.3
作者：
Jackson, M;Krassowska, A;Ramsahoye, B
通讯作者：
Ramsahoye, B