Replication timing maintains the global epigenetic state in human cells

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...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) Vol. 372; no. 6540; p. 371
Main Authors: Klein, Kyle N, Zhao, Peiyao A, Lyu, Xiaowen, Sasaki, Takayo, Bartlett, Daniel A, Singh, Amar M, Tasan, Ipek, Zhang, Meng, Watts, Lotte P, Hiraga, Shin-Ichiro, Natsume, Toyoaki, Zhou, Xuemeng, Baslan, Timour, Leung, Danny, Kanemaki, Masato T, Donaldson, Anne D, Zhao, Huimin, Dalton, Stephen, Corces, Victor G, Gilbert, David M
Format: Journal Article
Language:English
Published: United States 23.04.2021
Subjects:
Cell Line
Chromatin - metabolism
Chromatin Assembly and Disassembly
DNA Replication
DNA Replication Timing
Epigenesis, Genetic
Epigenome
Gene Expression
Gene Knockout Techniques
Genome, Human
Heterochromatin - metabolism
Histone Code
Histones - metabolism
Humans
Telomere-Binding Proteins - genetics
Telomere-Binding Proteins - metabolism
ISSN:1095-9203, 1095-9203
Online Access:Get more information
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Summary: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.
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ISSN:1095-9203
1095-9203
DOI:10.1126/science.aba5545