Gadd45a promotes DNA demethylation through TDG | |
Li, Zheng; Gu, Tian-Peng; Weber, Alain R.; Shen, Jia-Zhen; Li, Bin-Zhong; Xie, Zhi-Guo; Yin, Ruichuan; Guo, Fan; Liu, Xiaomeng; Tang, Fuchou | |
刊名 | NUCLEIC ACIDS RESEARCH
![]() |
2015-04-30 | |
卷号 | 43期号:8页码:3986-3997 |
英文摘要 | Growth arrest and DNA-damage-inducible protein 45 (Gadd45) family members have been implicated in DNA demethylation in vertebrates. However, it remained unclear how they contribute to the demethylation process. Here, we demonstrate that Gadd45a promotes active DNA demethylation through thymine DNA glycosylase (TDG) which has recently been shown to excise 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) generated in Ten-eleven-translocation (Tet)-initiated oxidative demethylation. The connection of Gadd45a with oxidative demethylation is evidenced by the enhanced activation of a methylated reporter gene in HEK293T cells expressing Gadd45a in combination with catalytically active TDG and Tet. Gadd45a interacts with TDG physically and increases the removal of 5fC and 5caC from genomic and transfected plasmid DNA by TDG. Knockout of both Gadd45a and Gadd45b from mouse ES cells leads to hypermethylation of specific genomic loci most of which are also targets of TDG and show 5fC enrichment in TDG-deficient cells. These observations indicate that the demethylation effect of Gadd45a is mediated by TDG activity. This finding thus unites Gadd45a with the recently defined Tet-initiated demethylation pathway. |
研究领域[WOS] | Biochemistry & Molecular Biology |
WOS记录号 | WOS:000355317200017 |
公开日期 | 2016-03-15 |
内容类型 | 期刊论文 |
源URL | [http://ir.rcees.ac.cn/handle/311016/32582] ![]() |
专题 | 生态环境研究中心_环境化学与生态毒理学国家重点实验室 |
推荐引用方式 GB/T 7714 | Li, Zheng,Gu, Tian-Peng,Weber, Alain R.,et al. Gadd45a promotes DNA demethylation through TDG[J]. NUCLEIC ACIDS RESEARCH,2015,43(8):3986-3997. |
APA | Li, Zheng.,Gu, Tian-Peng.,Weber, Alain R..,Shen, Jia-Zhen.,Li, Bin-Zhong.,...&Xu, Guo-Liang.(2015).Gadd45a promotes DNA demethylation through TDG.NUCLEIC ACIDS RESEARCH,43(8),3986-3997. |
MLA | Li, Zheng,et al."Gadd45a promotes DNA demethylation through TDG".NUCLEIC ACIDS RESEARCH 43.8(2015):3986-3997. |
个性服务 |
查看访问统计 |
相关权益政策 |
暂无数据 |
收藏/分享 |
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。
修改评论