Uracil-DNA Glycosylase UNG Promotes Tet-mediated DNA Demethylation
Xue, Jian-Huang1; Xu, Gui-Fang1,2; Gu, Tian-Peng1; Chen, Guo-Dong1; Han, Bin-Bin1; Xu, Zhi-Mei1; Bjoras, Magnar3; Krokan, Hans E.4; Xu, Guo-Liang1,5; Du, Ya-Rui1
2016-01-08
Source PublicationJOURNAL OF BIOLOGICAL CHEMISTRY
ISSN1083351X
Volume291Issue:2Pages:731-738
Status已发表
DOI10.1074/jbc.M115.693861
AbstractIn 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.
Indexed BySCI ; EI
Language英语
Funding ProjectBreakthrough Project of Strategic Priority Program of the Chinese Academy of Sciences[XDB13000000]
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000367830500021
PublisherAMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
EI Accession Number20160301814475
EI KeywordsAlkylation ; Aromatic compounds ; Cells ; Chemical reactions ; Cytology ; Mammals ; Methylation ; Stem cells ; Transcription
EI Classification NumberBiological Materials and Tissue Engineering:461.2 ; Biology:461.9 ; Chemical Reactions:802.2 ; Chemical Operations:802.3 ; Organic Compounds:804.1
WOS KeywordACTIVE-DEMETHYLATION ; CRYSTAL-STRUCTURE ; TDG ; 5-CARBOXYLCYTOSINE ; 5-FORMYLCYTOSINE ; 5-METHYLCYTOSINE ; METHYLATION ; OXIDATION ; EXCISION ; 5-HYDROXYMETHYLCYTOSINE
Original Document TypeArticle
Citation statistics
Cited Times:23[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttps://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1948
Collection生命科学与技术学院_特聘教授组_徐国良组
Corresponding AuthorDu, Ya-Rui
Affiliation1.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
Recommended Citation
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.
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