Gadd45a promotes DNA demethylation through TDG

CORC > 生态环境研究中心 > 中国科学院生态环境研究中心 > 环境化学与生态毒理学国家重点实验室

	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.