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

• Published in: Nature communications Vol. 11; no. 1; p. 1345
• Main Authors: Falbo, Lucia, Raspelli, Erica, Romeo, Francesco, Fiorani, Simona, Pezzimenti, Federica, Casagrande, Francesca, Costa, Ilaria, Parazzoli, Dario, Costanzo, Vincenzo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12-03-2020; Nature Publishing Group; Nature Portfolio
• Subjects: 631/80/641/151; 631/80/641/151/1431; 64/114; 82/1; 82/29; 82/83; Animals; Assembly; Blastula; Blastula - embryology; Blastula - metabolism; Cell cycle; Chromatin - genetics; Chromatin - metabolism; Chromatin remodeling; Density; Deoxyribonucleic acid; DNA; DNA biosynthesis; DNA Replication; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Embryogenesis; Embryonic growth stage; Embryos; Genomes; High Mobility Group Proteins; Histone H1; Histones; Histones - chemistry; Histones - genetics; Histones - metabolism; Humanities and Social Sciences; multidisciplinary; Nuclei; Protein Domains; Replication; Replication Origin; Replication origins; Reproduction (copying); Science; Science (multidisciplinary); Vertebrates; Xenopus laevis; Xenopus laevis - embryology; Xenopus laevis - genetics; Xenopus laevis - metabolism; Xenopus Proteins - genetics; Xenopus Proteins - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-15180-5

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.
During embryonic development, it is vital to maintain rapid genome duplication. Here, the authors shed light on the mechanism by revealing that SSRP1 stimulates replication origin assembly on somatic nuclei in
Xenopus laevis
egg extract by promoting histone H1 eviction from somatic chromatin.