Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine.

Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine.
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DOI:
10.1126/science.1210597
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发表时间:
2011-09-02
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Zhang Y
Zhang Y
中科院分区:
其他
文献类型:
--
作者:
Ito S;Shen L;Dai Q;Wu SC;Collins LB;Swenberg JA;He C;Zhang Y

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DNA中的5-甲基胞嘧啶(5mC)在基因表达、基因组印迹和转座因子的抑制中起着重要作用。5mC可被Tet蛋白转化为5-羟甲基胞嘧啶(5hmC)。本研究表明,除了5hmC外,Tet蛋白还能以酶活性依赖的方式从5mC生成5-甲酰基胞嘧啶(5fC)和5-羧基胞嘧啶(5caC)。此外,我们在小鼠胚胎干细胞和小鼠器官的基因组DNA中发现了5fC和5caC的存在。基因组中5hmC、5fC和5caC的含量可以通过Tet蛋白的过表达或缺失而增加或减少。因此,我们在基因组DNA中鉴定了两种新的胞嘧啶衍生物,作为Tet蛋白的产物。我们的研究提出了DNA去甲基化可能通过tet催化氧化和脱羧发生的可能性。
5-methylcytosine (5mC) in DNA plays an important role in gene expression, genomic imprinting, and suppression of transposable elements. 5mC can be converted to 5-hydroxymethylcytosine (5hmC) by the Tet proteins. Here we show that, in addition to 5hmC, the Tet proteins can generate 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) from 5mC in an enzymatic activity-dependent manner. Furthermore, we reveal the presence of 5fC and 5caC in genomic DNA of mouse ES cells and mouse organs. The genomic content of 5hmC, 5fC, and 5caC can be increased or reduced through overexpression or depletion of Tet proteins. Thus, we identify two new cytosine derivatives in genomic DNA as the products of Tet proteins. Our study raises the possibility that DNA demethylation may occur through Tet-catalyzed oxidation followed by decarboxylation.
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