Tet-mediated Formation of 5-carboxylcytosine and Its Excision by TDG in Mammalian DNA

Overview

Journal Science

Specialty Science

Date 2011 Aug 6

PMID 21817016

Citations 1375

Authors

Yu-Fei He

Bin-Zhong Li

Zheng Li

Peng Liu

Yang Wang

Qingyu Tang

Jianping Ding

Yingying Jia

Zhangcheng Chen

Lin Li

Yan Sun

Xiuxue Li

Qing Dai

Chun-Xiao Song

Kangling Zhang

Chuan He

Guo-Liang Xu

Affiliations

Soon will be listed here.

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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