期刊
NATURE COMMUNICATIONS
卷 9, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-018-05697-1
关键词
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资金
- la Ligue Nationale contre le Cancer (Equipe labellisee Ligue) [ANR-11-LABX-0044_DEEP, ANR-10-IDEX-0001-02, ANR-12-BSV5-0022-02, ANR-14-CE16-0009, ANR-14-CE10-0013]
- EU [678563, ERC-2015-ADG-694694, ANR-16-CE15-0018, ANR-16-CE12-0024, ANR-16-CE11-0028]
- Agence Nationale de la Recherche (Investissements d'Avenir program) [ANR-10-EQPX-03, ANR-10-INBS-09-08]
- Canceropole Ile-de-France
- SiRIC-Curie program-SiRIC Grant [INCa-DGOS- 4654]
- European Research Council (ERC) [678563] Funding Source: European Research Council (ERC)
- Agence Nationale de la Recherche (ANR) [ANR-14-CE10-0013] Funding Source: Agence Nationale de la Recherche (ANR)
DNA replication is a challenge for the faithful transmission of parental information to daughter cells, as both DNA and chromatin organization must be duplicated. Replication stress further complicates the safeguard of epigenome integrity. Here, we investigate the transmission of the histone variants H3.3 and H3.1 during replication. We follow their distribution relative to replication timing, first in the genome and, second, in 3D using super-resolution microscopy. We find that H3.3 and H3.1 mark early-and late-replicating chromatin, respectively. In the nucleus, H3.3 forms domains, which decrease in density throughout replication, while H3.1 domains increase in density. Hydroxyurea impairs local recycling of parental histones at replication sites. Similarly, depleting the histone chaperone ASF1 affects recycling, leading to an impaired histone variant landscape. We discuss how faithful transmission of histone variants involves ASF1 and can be impacted by replication stress, with ensuing consequences for cell fate and tumorigenesis.
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