SET8 prevents excessive DNA methylation by methylation-mediated degradation of UHRF1 and DNMT1
文献类型：期刊论文
| 作者 | Zhang, Huifang5; Gao, Qinqin2; Tan, Shuo5; You, Jia5; Lyu, Cong3; Zhang, Yunpeng5; Han, Mengmeng5; Chen, Zhaosu5; Li, Jialun5; Wang, Hailin3 |
| 刊名 | NUCLEIC ACIDS RESEARCH
 |
| 出版日期 | 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. |
| 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.Natl Ctr Prot Sci Beijing, Beijing Proteome Res Ctr, Inst Lifeom, State Key Lab Prote, Beijing 102206, Peoples R China 2.East China Normal Univ, Sch Life Sci, Shanghai 200241, Peoples R China 3.Soochow Univ, Hosp 1, Inst Fetol, Suzhou, Peoples R China 4.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing 100085, 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. |
入库方式： OAI收割
来源：生态环境研究中心
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