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Nat Commun January 1, 2020; 11 (1): 1345.

SSRP1-mediated histone H1 eviction promotes replication origin assembly and accelerated development.

Falbo L , Raspelli E , Romeo F , Fiorani S , Pezzimenti F , Casagrande F , Costa I , Parazzoli D , Costanzo V .

In several metazoans, the number of active replication origins in embryonic nuclei is higher than in somatic ones, ensuring rapid genome duplication during synchronous embryonic cell divisions. High replication origin density can be restored by somatic nuclear reprogramming. However, mechanisms underlying high replication origin density formation coupled to rapid cell cycles are poorly understood. Here, using Xenopus laevis, we show that SSRP1 stimulates replication origin assembly on somatic chromatin by promoting eviction of histone H1 through its N-terminal domain. Histone H1 removal derepresses ORC and MCM chromatin binding, allowing efficient replication origin assembly. SSRP1 protein decays at mid-blastula transition (MBT) when asynchronous somatic cell cycles start. Increasing levels of SSRP1 delay MBT and, surprisingly, accelerate post-MBT cell cycle speed and embryo development. These findings identify a major epigenetic mechanism regulating DNA replication and directly linking replication origin assembly, cell cycle duration and embryo development in vertebrates.

PubMed ID: 32165637
PMC ID: PMC7067836
Article link: Nat Commun
Grant support: [+]
Genes referenced: ctrl h2bc21 mcm7 mmut myc orc1 ssrp1
GO keywords: cell cycle

Article Images: [+] show captions

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