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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
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出版日期 | 2011-09-02 |
卷号 | 333期号:6047页码:1303-1307 |
ISSN号 | 0036-8075 |
DOI | 10.1126/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; |
推荐引用方式 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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