期刊
NUCLEIC ACIDS RESEARCH
卷 43, 期 12, 页码 5898-5911出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkv509
关键词
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资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [17080013, 21370084, 25291027, 26114713, 09J07233]
- Grants-in-Aid for Scientific Research [21370084, 17080013, 09J07233, 26290064, 25116010, 26114713, 15K18412] Funding Source: KAKEN
Efficient pre-replication complex (pre-RC) formation on chromatin templates is crucial for the maintenance of genome integrity. However, the regulation of chromatin dynamics during this process has remained elusive. We found that a conserved protein, GRWD1 (glutamate-rich WD40 repeat containing 1), binds to two representative replication origins specifically during G1 phase in a CDC6- and Cdt1-dependent manner, and that depletion of GRWD1 reduces loading of MCM but not CDC6 and Cdt1. Furthermore, chromatin immunoprecipitation coupled with high-throughput sequencing (Seq) revealed significant genome-wide co-localization of GRWD1 with CDC6. We found that GRWD1 has histone-binding activity. To investigate the effect of GRWD1 on chromatin architecture, we used formaldehyde-assisted isolation of regulatory elements (FAIRE)-seq or FAIRE-quantitative PCR analyses, and the results suggest that GRWD1 regulates chromatin openness at specific chromatin locations. Taken together, these findings suggest that GRWD1 may be a novel histone-binding protein that regulates chromatin dynamics and MCM loading at replication origins.
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