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

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SSRP1-mediated histone H1 eviction promotes replication origin assembly and accelerated development.
Nature Communications ( IF 14.7 ) Pub Date : 2020-03-12 , DOI: 10.1038/s41467-020-15180-5
Lucia Falbo ₁ , Erica Raspelli ₁ , Francesco Romeo ₁ , Simona Fiorani ₂ , Federica Pezzimenti ₁ , Francesca Casagrande ₁ , Ilaria Costa ₁ , Dario Parazzoli ₁ , Vincenzo Costanzo _{1,

3}

Affiliation

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.

中文翻译：

SSRP1介导的组蛋白H1驱逐促进了复制起点的组装并加速了发育。

在一些后生动物中，胚胎核中主动复制起源的数量高于体细胞中的复制起源，从而确保了同步胚胎细胞分裂期间基因组的快速复制。高复制起点密度可以通过体细胞核重编程来恢复。但是，对高复制起点密度形成与快速细胞周期偶联的机制了解得很少。在这里，我们使用非洲爪蟾，表明SSRP1通过促进通过其N端域驱逐组蛋白H1刺激体染色质上的复制起点组装。去除组蛋白H1可抑制ORC和MCM染色质结合，从而实现有效的复制起点组装。当异步体细胞周期开始时，SSRP1蛋白在中胚层过渡期（MBT）衰减。SSRP1水平的增加延迟了MBT，令人惊讶的是，加快MBT后细胞的周期速度和胚胎发育。这些发现确定了脊椎动物中调控DNA复制并将复制起点装配，细胞周期持续时间和胚胎发育直接联系在一起的主要表观遗传机制。

更新日期：2020-03-12

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