Tet-Mediated Formation of 5-Carboxylcytosine and Its Excision by TDG in Mammalian DNA
He, Yu-Fei; Li, Bin-Zhong; Li, Zheng; Liu, Peng; Wang, Yang; Tang, Qingyu; Ding, Jianping; Jia, Yingying; Chen, Zhangcheng; Li, Lin; Sun, Yan; Li, Xiuxue; Dai, Qing; Song, Chun-Xiao; Zhang, Kangling; He, Chuan; Xu, Guo-Liang
2011
Source PublicationSCIENCE
ISSN0036-8075
Volume333Issue:6047Pages:133-137
Status已发表
DOI10.1126/science.1210944
Abstract

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.

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Indexed BySCI
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000294406400058
PublisherAMER ASSOC ADVANCEMENT SCIENCE
WOS KeywordEMBRYONIC STEM-CELLS ; GLYCOSYLASE ACTIVITY ; GENE-EXPRESSION ; 5-HYDROXYMETHYLCYTOSINE ; DEMETHYLATION ; METHYLATION ; REPAIR ; DEAMINATION
Original Document TypeArticle
Citation statistics
Cited Times:1741[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttps://kms.shanghaitech.edu.cn/handle/2MSLDSTB/119804
Collection个人在本单位外知识产出
Corresponding AuthorXu, Guo-Liang
Affiliation1.Chinese Acad Sci, Grp DNA Metab, State Key Lab Mol Biol, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China
2.Chinese Acad Sci, Inst Mat Med, Shanghai 201203, Peoples R China
3.Univ Chicago, Dept Chem, Chicago, IL 60637 USA
4.Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA
5.Loma Linda Univ, Sch Med, Dept Biochem, Loma Linda, CA 92350 USA
Recommended Citation
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):133-137.
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),133-137.
MLA He, Yu-Fei,et al."Tet-Mediated Formation of 5-Carboxylcytosine and Its Excision by TDG in Mammalian DNA".SCIENCE 333.6047(2011):133-137.
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