Kinetics and mechanisms of mitotic inheritance of DNA methylation and their roles in aging-associated methylome deterioration

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

	Kinetics and mechanisms of mitotic inheritance of DNA methylation and their roles in aging-associated methylome deterioration
	Ming, Xuan; Zhang, Zhuqiang; Zou, Zhuoning; Lv, Cong; Dong, Qiang; He, Qixiang; Yi, Yangyang; Li, Yingfeng; Wang, Hailin; Zhu, Bing
刊名	CELL RESEARCH
	2020-11
卷号	30 期号:11 页码:980-996
ISSN号	1001-0602
英文摘要	Mitotic inheritance of the DNA methylome is a challenging task for the maintenance of cell identity. Whether DNA methylation pattern in different genomic contexts can all be faithfully maintained is an open question. A replication-coupled DNA methylation maintenance model was proposed decades ago, but some observations suggest that a replication-uncoupled maintenance mechanism exists. However, the capacity and the underlying molecular events of replication-uncoupled maintenance are unclear. By measuring maintenance kinetics at the single-molecule level and assessing mutant cells with perturbation of various mechanisms, we found that the kinetics of replication-coupled maintenance are governed by the UHRF1-Ligase 1 and PCNA-DNMT1 interactions, whereas nucleosome occupancy and the interaction between UHRF1 and methylated H3K9 specifically regulate replication-uncoupled maintenance. Surprisingly, replication-uncoupled maintenance is sufficiently robust to largely restore the methylome when replication-coupled maintenance is severely impaired. However, solo-WCGW sites and other CpG sites displaying aging- and cancer-associated hypomethylation exhibit low maintenance efficiency, suggesting that although quite robust, mitotic inheritance of methylation is imperfect and that this imperfection may contribute to selective hypomethylation during aging and tumorigenesis.
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/44720]
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
推荐引用方式 GB/T 7714	Ming, Xuan,Zhang, Zhuqiang,Zou, Zhuoning,et al. Kinetics and mechanisms of mitotic inheritance of DNA methylation and their roles in aging-associated methylome deterioration[J]. CELL RESEARCH,2020,30(11):980-996.
APA	Ming, Xuan.,Zhang, Zhuqiang.,Zou, Zhuoning.,Lv, Cong.,Dong, Qiang.,...&Zhu, Bing.(2020).Kinetics and mechanisms of mitotic inheritance of DNA methylation and their roles in aging-associated methylome deterioration.CELL RESEARCH,30(11),980-996.
MLA	Ming, Xuan,et al."Kinetics and mechanisms of mitotic inheritance of DNA methylation and their roles in aging-associated methylome deterioration".CELL RESEARCH 30.11(2020):980-996.