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Tet-Mediated Formation of 5-Carboxylcytosine and Its Excision by TDG in Mammalian DNA

文献类型:期刊论文

作者He, Yu-Fei5; Li, Bin-Zhong5; Li, Zheng5; Liu, Peng5; Wang, Yang5; Tang, Qingyu; Ding, Jianping; Jia, Yingying; Chen, Zhangcheng; Li, Lin
刊名SCIENCE
出版日期2011-09-02
卷号333期号:6047页码:1303-1307
ISSN号0036-8075
DOI10.1126/science.1210944
文献子类Article
英文摘要The prevalent DNA modification in higher organisms is the methylation of cytosine to 5-methylcytosine (5mC), which is partially converted to 5-hydroxymethylcytosine (5hmC) by the Tet (ten eleven translocation) family of dioxygenases. Despite their importance in epigenetic regulation, it is unclear how these cytosine modifications are reversed. Here, we demonstrate that 5mC and 5hmC in DNA are oxidized to 5-carboxylcytosine (5caC) by Tet dioxygenases in vitro and in cultured cells. 5caC is specifically recognized and excised by thymine-DNA glycosylase (TDG). Depletion of TDG in mouse embyronic stem cells leads to accumulation of 5caC to a readily detectable level. These data suggest that oxidation of 5mC by Tet proteins followed by TDG-mediated base excision of 5caC constitutes a pathway for active DNA demethylation.
WOS关键词EMBRYONIC STEM-CELLS ; GLYCOSYLASE ACTIVITY ; GENE-EXPRESSION ; 5-HYDROXYMETHYLCYTOSINE ; DEMETHYLATION ; METHYLATION ; REPAIR ; DEAMINATION
资助项目Ministry of Science and Technology China[2007CB947503] ; Ministry of Science and Technology China[2009CB941101] ; Ministry of Science and Technology China[2010CB912100] ; National Science Foundation of China[30730059] ; National Science Foundation of China[30930052] ; National Science Foundation of China[30821065] ; Chinese Academy of Sciences[XDA01010301] ; NIH[GM071440] ; NIH[1S10RR027643-01]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000294406400058
出版者AMER ASSOC ADVANCEMENT SCIENCE
源URL[http://119.78.100.183/handle/2S10ELR8/278408]  
专题上海药物代谢研究中心
通讯作者Xu, Guo-Liang
作者单位1.Loma Linda Univ, Sch Med, Dept Biochem, Loma Linda, CA 92350 USA
2.Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA;
3.Univ Chicago, Dept Chem, Chicago, IL 60637 USA;
4.Chinese Acad Sci, Inst Mat Med, Shanghai 201203, Peoples R China;
5.Chinese Acad Sci, Grp DNA Metab, State Key Lab Mol Biol, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China;
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GB/T 7714
He, Yu-Fei,Li, Bin-Zhong,Li, Zheng,et al. Tet-Mediated Formation of 5-Carboxylcytosine and Its Excision by TDG in Mammalian DNA[J]. SCIENCE,2011,333(6047):1303-1307.
APA He, Yu-Fei.,Li, Bin-Zhong.,Li, Zheng.,Liu, Peng.,Wang, Yang.,...&Xu, Guo-Liang.(2011).Tet-Mediated Formation of 5-Carboxylcytosine and Its Excision by TDG in Mammalian DNA.SCIENCE,333(6047),1303-1307.
MLA He, Yu-Fei,et al."Tet-Mediated Formation of 5-Carboxylcytosine and Its Excision by TDG in Mammalian DNA".SCIENCE 333.6047(2011):1303-1307.

入库方式: OAI收割

来源:上海药物研究所

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