Uracil-DNA Glycosylase UNG Promotes Tet-mediated DNA Demethylation

doi:10.1074/jbc.M115.693861

	Uracil-DNA Glycosylase UNG Promotes Tet-mediated DNA Demethylation
	Xue, Jian-Huang 1; Xu, Gui-Fang 1,2; Gu, Tian-Peng 1; Chen, Guo-Dong 1; Han, Bin-Bin 1; Xu, Zhi-Mei 1; Bjoras, Magnar 3; Krokan, Hans E.4; Xu, Guo-Liang1,5 ; Du, Ya-Rui 1
	2016-01-08
发表期刊	JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN	1083351X
卷号	291 期号:2 页码:731-738
发表状态	已发表
DOI	10.1074/jbc.M115.693861
摘要	In mammals, active DNA demethylation involves oxidation of 5-methylcytosine (5mC) into 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) by Tet dioxygenases and excision of these two oxidized bases by thymine DNA glycosylase (TDG). Although TDG is essential for active demethylation in embryonic stem cells and induced pluripotent stem cells, it is hardly expressed in mouse zygotes and dispensable in pronuclear DNA demethylation. To search for other factors that might contribute to demethylation in mammalian cells, we performed a functional genomics screen based on a methylated luciferase reporter assay. UNG2, one of the glycosylases known to excise uracil residues from DNA, was found to reduce DNA methylation, thus activating transcription of a methylation-silenced reporter gene when co-transfected with Tet2 into HEK293T cells. Interestingly, UNG2 could decrease 5caC from the genomic DNA and a reporter plasmid in transfected cells, like TDG. Furthermore, deficiency in Ung partially impaired DNA demethylation in mouse zygotes. Our results suggest that UNG might be involved in Tet-mediated DNA demethylation.
收录类别	SCI ; EI
语种	英语
资助项目	Breakthrough Project of Strategic Priority Program of the Chinese Academy of Sciences[XDB13000000]
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
WOS记录号	WOS:000367830500021
出版者	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
EI入藏号	20160301814475
EI主题词	Alkylation ; Aromatic compounds ; Cells ; Chemical reactions ; Cytology ; Mammals ; Methylation ; Stem cells ; Transcription
EI分类号	Biological Materials and Tissue Engineering:461.2 ; Biology:461.9 ; Chemical Reactions:802.2 ; Chemical Operations:802.3 ; Organic Compounds:804.1
WOS关键词	ACTIVE-DEMETHYLATION ; CRYSTAL-STRUCTURE ; TDG ; 5-CARBOXYLCYTOSINE ; 5-FORMYLCYTOSINE ; 5-METHYLCYTOSINE ; METHYLATION ; OXIDATION ; EXCISION ; 5-HYDROXYMETHYLCYTOSINE
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1948
专题	生命科学与技术学院_特聘教授组_徐国良组
通讯作者	Du, Ya-Rui
作者单位	1.Chinese Acad Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China 2.Fudan Univ, Sch Life Sci, Shanghai 200433, Peoples R China 3.Natl Hosp Norway, Oslo Univ Hosp, Clin Diagnost & Intervent, Dept Microbiol, N-0424 Oslo, Norway 4.Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, NO-7491 Trondheim, Norway 5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China
推荐引用方式 GB/T 7714	Xue, Jian-Huang,Xu, Gui-Fang,Gu, Tian-Peng,et al. Uracil-DNA Glycosylase UNG Promotes Tet-mediated DNA Demethylation[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2016,291(2):731-738.
APA	Xue, Jian-Huang.,Xu, Gui-Fang.,Gu, Tian-Peng.,Chen, Guo-Dong.,Han, Bin-Bin.,...&Du, Ya-Rui.(2016).Uracil-DNA Glycosylase UNG Promotes Tet-mediated DNA Demethylation.JOURNAL OF BIOLOGICAL CHEMISTRY,291(2),731-738.
MLA	Xue, Jian-Huang,et al."Uracil-DNA Glycosylase UNG Promotes Tet-mediated DNA Demethylation".JOURNAL OF BIOLOGICAL CHEMISTRY 291.2(2016):731-738.