SET8 prevents excessive DNA methylation by methylation-mediated degradation of UHRF1 and DNMT1

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

	SET8 prevents excessive DNA methylation by methylation-mediated degradation of UHRF1 and DNMT1
	Zhang, Huifang 5; Gao, Qinqin 4; Tan, Shuo 5; You, Jia 5; Lyu, Cong 1; Zhang, Yunpeng 5; Han, Mengmeng 5; Chen, Zhaosu 5; Li, Jialun 5; Wang, Hailin 1
刊名	NUCLEIC ACIDS RESEARCH
	2019-09-26
卷号	47 期号:17 页码:9053-9068
ISSN号	0305-1048
英文摘要	Faithful inheritance of DNA methylation across cell division requires DNMT1 and its accessory factor UHRF1. However, how this axis is regulated to ensure DNA methylation homeostasis remains poorly understood. Here we show that SET8, a cell-cycle-regulated protein methyltransferase, controls protein stability of both UHRF1 and DNMT1 through methylation-mediated, ubiquitin-dependent degradation and consequently prevents excessive DNA methylation. SET8 methylates UHRF1 at lysine 385 and this modification leads to ubiquitination and degradation of UHRF1. In contrast, LSD1 stabilizes both UHRF1 and DNMT1 by demethylation. Importantly, SET8 and LSD1 oppositely regulate global DNA methylation and do so most likely through regulating the level of UHRF1 than DNMT1. Finally, we show that UHRF1 downregulation in G2/M by SET8 has a role in suppressing DNMT1-mediated methylation on post-replicated DNA. Altogether, our study reveals a novel role of SET8 in promoting DNA methylation homeostasis and identifies UHRF1 as the hub for tuning DNA methylation through dynamic protein methylation.
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/42588]
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
作者单位	1.Soochow Univ, Hosp 1, Inst Fetol, Suzhou, Peoples R China 2.Natl Ctr Prot Sci Beijing, Beijing Proteome Res Ctr, Inst Lifeom, State Key Lab Prote, Beijing 102206, Peoples R China 3.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing 100085, Peoples R China 4.East China Normal Univ, Sch Life Sci, Shanghai 200241, Peoples R China 5.East China Normal Univ, Shanghai Key Lab Regulatory Biol, Fengxian Dist Cent Hosp, ECNU Joint Ctr Translat Med,Inst Biomed Sci, Shanghai 200241, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Huifang,Gao, Qinqin,Tan, Shuo,et al. SET8 prevents excessive DNA methylation by methylation-mediated degradation of UHRF1 and DNMT1[J]. NUCLEIC ACIDS RESEARCH,2019,47(17):9053-9068.
APA	Zhang, Huifang.,Gao, Qinqin.,Tan, Shuo.,You, Jia.,Lyu, Cong.,...&Wong, Jiemin.(2019).SET8 prevents excessive DNA methylation by methylation-mediated degradation of UHRF1 and DNMT1.NUCLEIC ACIDS RESEARCH,47(17),9053-9068.
MLA	Zhang, Huifang,et al."SET8 prevents excessive DNA methylation by methylation-mediated degradation of UHRF1 and DNMT1".NUCLEIC ACIDS RESEARCH 47.17(2019):9053-9068.