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Sperm derived H2AK119ub1 is required for embryonic development in Xenopus laevis

Valentin Francois--Campion, Florian Berger, Mami Oikawa, Maissa Goumeidane, Nolwenn Mouniée, Vanessa Chenouard, Kseniya Petrova, Jose G. Abreu, Cynthia Fourgeux, Jeremie Poschmann, Leonid Peshkin, Romain Gibeaux and Jérôme Jullien ()
Additional contact information
Valentin Francois--Campion: UMR 1064
Florian Berger: UMR 1064
Mami Oikawa: Hachioji
Maissa Goumeidane: UMR 1064
Nolwenn Mouniée: UMR 1064
Vanessa Chenouard: UMR 1064
Kseniya Petrova: Harvard Medical School
Jose G. Abreu: Harvard Medical School
Cynthia Fourgeux: UMR 1064
Jeremie Poschmann: UMR 1064
Leonid Peshkin: Harvard Medical School
Romain Gibeaux: IGDR (Institut de Génétique et Développement de Rennes) - UMR 6290
Jérôme Jullien: UMR 1064

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Ubiquitylation of H2A (H2AK119ub1) by the polycomb repressive complexe-1 plays a key role in the initiation of facultative heterochromatin formation in somatic cells. Here we evaluate the contribution of sperm derived H2AK119ub1 to embryo development. In Xenopus laevis we found that H2AK119ub1 is present during spermiogenesis and into early embryonic development, highlighting its credential for a role in the transmission of epigenetic information from the sperm to the embryo. In vitro treatment of sperm with USP21, a H2AK119ub1 deubiquitylase, just prior to injection to egg, results in developmental defects associated with gene upregulation. Sperm H2AK119ub1 editing disrupts egg factor mediated paternal chromatin remodelling processes. It leads to post-replication accumulation of H2AK119ub1 on repeat element of the genome instead of CpG islands. This shift in post-replication H2AK119ub1 distribution triggered by sperm epigenome editing entails a loss of H2AK119ub1 from genes misregulated in embryos derived from USP21 treated sperm. We conclude that sperm derived H2AK119ub1 instructs egg factor mediated epigenetic remodelling of paternal chromatin and is required for embryonic development.

Date: 2025
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DOI: 10.1038/s41467-025-58615-7

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