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DOI10.1126/science.aba5545
Replication timing maintains the global epigenetic state in human cells
Kyle N. Klein; Peiyao A. Zhao; Xiaowen Lyu; Takayo Sasaki; Daniel A. Bartlett; Amar M. Singh; Ipek Tasan; Meng Zhang; Lotte P. Watts; Shin-ichiro Hiraga; Toyoaki Natsume; Xuemeng Zhou; Timour Baslan; Danny Leung; Masato T. Kanemaki; Anne D. Donaldson; Huimin Zhao; Stephen Dalton; Victor G. Corces; David M. Gilbert
2021-04-23
发表期刊Science
出版年2021
英文摘要The temporal order of DNA replication is conserved from yeast to humans, but its biological significance remains unclear. Klein et al. eliminated the protein RIF1, a master regulator of replication timing, in several human cell lines. RIF1 loss during the G1 phase of the cell cycle resulted in a heterogeneous, nearly random replication timing program from the first S phase that persisted even in stable RIF1-null clones. Altered replication timing was followed by replication-dependent redistribution of active and repressive histone modifications and alterations in genome architecture. These results support a model in which replication timing orchestrates the epigenetic state of newly replicated chromatin. Science , this issue p. [371][1] The temporal order of DNA replication [replication timing (RT)] is correlated with chromatin modifications and three-dimensional genome architecture; however, causal links have not been established, largely because of an inability to manipulate the global RT program. We show that loss of RIF1 causes near-complete elimination of the RT program by increasing heterogeneity between individual cells. RT changes are coupled with widespread alterations in chromatin modifications and genome compartmentalization. Conditional depletion of RIF1 causes replication-dependent disruption of histone modifications and alterations in genome architecture. These effects were magnified with successive cycles of altered RT. These results support models in which the timing of chromatin replication and thus assembly plays a key role in maintaining the global epigenetic state. [1]: /lookup/doi/10.1126/science.aba5545
领域气候变化 ; 资源环境
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文献类型期刊论文
条目标识符http://119.78.100.173/C666/handle/2XK7JSWQ/324076
专题气候变化
资源环境科学
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Kyle N. Klein,Peiyao A. Zhao,Xiaowen Lyu,et al. Replication timing maintains the global epigenetic state in human cells[J]. Science,2021.
APA Kyle N. Klein.,Peiyao A. Zhao.,Xiaowen Lyu.,Takayo Sasaki.,Daniel A. Bartlett.,...&David M. Gilbert.(2021).Replication timing maintains the global epigenetic state in human cells.Science.
MLA Kyle N. Klein,et al."Replication timing maintains the global epigenetic state in human cells".Science (2021).
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