Replication timing maintains the global epigenetic state in human cells Journal Article
| Authors: | Klein, K. N.; Zhao, P. A.; Lyu, X.; Sasaki, T.; Bartlett, D. A.; Singh, A. M.; Tasan, I.; Zhang, M.; Watts, L. P.; Hiraga, S. I.; Natsume, T.; Zhou, X.; Baslan, T.; Leung, D.; Kanemaki, M. T.; Donaldson, A. D.; Zhao, H.; Dalton, S.; Corces, V. G.; Gilbert, D. M. |
| Article Title: | Replication timing maintains the global epigenetic state in human cells |
| Abstract: | 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. © 2021 American Association for the Advancement of Science. All rights reserved. |
| Keywords: | genetics; dna replication; metabolism; gene expression; cell line; histone; chromatin; epigenesis, genetic; human genome; genetic epigenesis; histones; genome, human; heterochromatin; chromatin assembly and disassembly; gene knockout techniques; telomere-binding proteins; telomere binding protein; dna replication timing; histone code; epigenome; humans; human; gene knockout; rif1 protein, human |
| Journal Title: | Science |
| Volume: | 372 |
| Issue: | 6540 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2021-04-23 |
| Start Page: | 371 |
| End Page: | 378 |
| Language: | English |
| DOI: | 10.1126/science.aba5545 |
| PUBMED: | 33888635 |
| PROVIDER: | scopus |
| PMCID: | PMC8173839 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 June 2021 -- Source: Scopus |
