Tet Proteins Can Convert 5-Methylcytosine to 5-Formylcytosine and 5-Carboxylcytosine

被引：2578

作者：

Ito, Shinsuke ^{[1
,2
,3
]}

Shen, Li ^{[1
,2
,3
]}

Dai, Qing ^{[4
,5
]}

Wu, Susan C. ^{[1
,2
,3
]}

Collins, Leonard B. ^{[6
]}

Swenberg, James A. ^{[3
,6
]}

He, Chuan ^{[4
,5
]}

Zhang, Yi ^{[1
,2
,3
]}

机构：

[1] Univ N Carolina, Howard Hughes Med Inst, Chapel Hill, NC 27599 USA

[2] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA

[3] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[4] Univ Chicago, Dept Chem, Chicago, IL 60637 USA

[5] Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA

[6] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA

来源：

SCIENCE | 2011年 / 333卷 / 6047期

关键词：

ACTIVE DNA DEMETHYLATION; 5-HYDROXYMETHYLCYTOSINE;

D O I：

10.1126/science.1210597

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 (ten eleven translocation) 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 embryonic stem 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 previously unknown 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.

引用

页码：1300 / 1303

页数：4

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