Negative regulation of DNMT3A de novo DNA methylation by frequently overexpressed UHRF family proteins as a mechanism for widespread DNA hypomethylation in cancer

doi:10.1038/celldisc.2016.7

	Negative regulation of DNMT3A de novo DNA methylation by frequently overexpressed UHRF family proteins as a mechanism for widespread DNA hypomethylation in cancer
	Jia, Yuanhui 1,2; Li, Pishun 1,2; Fang, Lan 1,2; Zhu, Haijun 1,2; Xu, Liangliang 1,2; Cheng, Hao 3; Zhang, Junying 1,2; Li, Fei4,5,6,7 ; Feng, Yan 4,5,6,7; Li, Yan 8,9; Li, Jialun 1,2; Wang, Ruiping 1,2; Du, James X.1,2; Li, Jiwen 1,2; Chen, Taiping 8,9; Ji, Hongbin4,5,6,7 ; Han, Jackie 3; Yu, Wenqiang 10; Wu, Qihan 1,2; Wong, Jiemin 1,2,11
	2016-04-12
发表期刊	CELL DISCOVERY
ISSN	2056-5968
卷号	2
发表状态	已发表
DOI	10.1038/celldisc.2016.7
摘要	Global DNA hypomethylation is a most common epigenetic alteration in cancer, but the mechanism remains elusive. Previous studies demonstrate that UHRF1 but not UHRF2 is required for mediating DNA maintenance methylation by DNMT1. Here we report unexpectedly a conserved function for UHRF1 and UHRF2: inhibiting de novo DNA methylation by functioning as E3 ligases promoting DNMT3A degradation. UHRF1/2 are frequently overexpressed in cancers and we present evidence that UHRF1/2 overexpression downregulates DNMT3A proteins and consequently leads to DNA hypomethylation. Abrogating this negative regulation on DNMT3A or overexpression of DNMT3A leads to increased DNA methylation and impaired tumor growth. We propose a working model that UHRF1/2 safeguards the fidelity of DNA methylation and suggests that UHRF1/2 overexpression is likely a causal factor for widespread DNA hypomethylation in cancer via suppressing DNMT3A.
关键词	cancer DNA DNMT1 DNMT3A hypomethylation UHRF1 UHRF2
收录类别	SCI
语种	英语
资助项目	Science Technology Commission of Shanghai Municipality[14xD1401700] ; Science Technology Commission of Shanghai Municipality[11DZ2260300]
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000414793300001
出版者	NATURE PUBLISHING GROUP
WOS关键词	EMBRYONIC STEM-CELLS ; UBIQUITIN LIGASE ACTIVITY ; NUCLEAR-PROTEIN ; HISTONE-BINDING ; HUMAN-TUMORS ; SRA DOMAIN ; RNA-SEQ ; GENE ; METHYLTRANSFERASES ; MAINTENANCE
原始文献类型	Article
引用统计	被引频次：68[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/10051
专题	iHuman研究所_公共科研平台_IT平台生命科学与技术学院_特聘教授组_季红斌组
通讯作者	Wong, Jiemin
作者单位	1.East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Shanghai, Peoples R China 2.East China Normal Univ, Sch Life Sci, Shanghai, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Biol Sci, Chinese Acad Sci Max Planck Partner Inst Computat, Key Lab Computat Biol, Shanghai, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Key Lab Syst Biol, Shanghai, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, CAS Ctr Excellence Mol Cell Sci, Shanghai, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Innovat Ctr Cell Signaling Network, Shanghai, Peoples R China 7.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 8.Fudan Univ, Inst Biomed Sci, Lab RNA Epigenet, Shanghai, Peoples R China 9.Fudan Univ, Shanghai Med Coll, Dept Biochem & Mol Biol, Shanghai, Peoples R China 10.Univ Texas MD Anderson Canc Ctr, Dept Mol Carcinogenesis, Smithville, TX USA 11.Sun Yat Sen Univ, Ctr Canc, Collaborat Innovat Ctr Canc Med, Guangzhou, Guangdong, Peoples R China
推荐引用方式 GB/T 7714	Jia, Yuanhui,Li, Pishun,Fang, Lan,et al. Negative regulation of DNMT3A de novo DNA methylation by frequently overexpressed UHRF family proteins as a mechanism for widespread DNA hypomethylation in cancer[J]. CELL DISCOVERY,2016,2.
APA	Jia, Yuanhui.,Li, Pishun.,Fang, Lan.,Zhu, Haijun.,Xu, Liangliang.,...&Wong, Jiemin.(2016).Negative regulation of DNMT3A de novo DNA methylation by frequently overexpressed UHRF family proteins as a mechanism for widespread DNA hypomethylation in cancer.CELL DISCOVERY,2.
MLA	Jia, Yuanhui,et al."Negative regulation of DNMT3A de novo DNA methylation by frequently overexpressed UHRF family proteins as a mechanism for widespread DNA hypomethylation in cancer".CELL DISCOVERY 2(2016).