Replication-dependent loss of 5-hydroxymethylcytosine in mouse preimplantation embryos.
Replication-dependent loss of 5-hydroxymethylcytosine in mouse preimplantation embryos.
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DOI：
10.1126/science.1212483
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发表时间：
2011-10-14
期刊：
影响因子：
--
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Inoue A;Zhang Y
尽管在受精卵和原始生殖细胞中已经观察到DNA甲基化的全局擦除，但负责的酶一直难以捉摸。泰特（10 - 11易位）蛋白家族成员能够催化DNA的5-甲基胞嘧啶（5 mC）转化为5-羟甲基胞嘧啶（5 hmC）的证明提高了泰特蛋白可能参与该过程的可能性。事实上，最近的研究表明Tet 3参与了受精卵中5 mC向5 hmC的转化。这一结果，结合证明泰特蛋白可以进一步氧化5 hmC为5-carboxylcytosine随后切除的胸腺嘧啶-DNA糖基化酶，提出了主动去甲基化的可能性，可能发生在一个过程中，涉及泰特3介导的氧化，随后碱基切除修复。我们通过对植入前胚胎的有丝分裂染色体扩散的免疫染色表明，在植入前发育过程中，与受精卵中父亲基因组相关的5 hmC逐渐丢失。我们的研究表明，虽然5 mC到5 hmC在受精卵中的转换是一个酶催化的过程，5 hmC在植入前的损失似乎是一个DNA复制依赖的被动过程。
Although global erasure of DNA methylation has been observed in zygotes and primordial germ cells, the responsible enzyme(s) have been elusive. The demonstration that members of the Tet (ten eleven translocation) family of proteins are capable of catalyzing conversion of 5-methylcytosine (5mC) of DNA to 5-hydroxymethylcytosine (5hmC) raises the possibility that Tet proteins may participate in this process. Indeed, recent studies have implicated the involvement of Tet3 in the conversion of 5mC to 5hmC in zygotes. This result, combined with the demonstration that Tet proteins can further oxidize 5hmC to 5-carboxylcytosine followed by excision by thymine-DNA glycosylase, raises the possibility that active demethylation may take place in a process that involves Tet3-mediated oxidation followed by base excision repair. We demonstrated by immunostaining of mitotic chromosome spreads of preimplantation embryos that the 5hmC associated with the paternal genome in zygotes is gradually lost during preimplantation development. Our study suggests that, although the conversion of 5mC to 5hmC in zygotes is an enzyme-catalyzed process, loss of 5hmC during preimplantation appears to be a DNA replication–dependent passive process.
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DOI：
10.1126/science.1170116
发表时间：
2009-05-15
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
Tahiliani M;Koh KP;Shen Y;Pastor WA;Bandukwala H;Brudno Y;Agarwal S;Iyer LM;Liu DR;Aravind L;Rao A
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DOI：
10.1038/nrm2950
发表时间：
2010-09
期刊：
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哺乳动物 DNA 中 Tet 介导的 5-羧基胞嘧啶的形成及其 TDG 的切除
DOI：
10.1126/science.1210944
发表时间：
2011-09-02
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
He YF;Li BZ;Li Z;Liu P;Wang Y;Tang Q;Ding J;Jia Y;Chen Z;Li L;Sun Y;Li X;Dai Q;Song CX;Zhang K;He C;Xu GL
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DOI：
10.1073/pnas.1014033108
发表时间：
2011-03-01
影响因子：
11.1
作者：
Iqbal, Khursheed;Jin, Seung-Gi;Szabo, Piroska E.
通讯作者：
Szabo, Piroska E.