Francois-Campion Valentin, Berger Florian, Oikawa Mami, Goumeidane Maissa, Mouniée Nolwenn, Chenouard Vanessa, Petrova Kseniya, Abreu Jose G, Fourgeux Cynthia, Poschmann Jeremie, Peshkin Leonid, Gibeaux Romain, Jullien Jérôme
Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France.
Laboratory of Regenerative Medicine, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo, Japan.
Nat Commun. 2025 Apr 5;16(1):3268. doi: 10.1038/s41467-025-58615-7.
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.
多梳抑制复合物-1对组蛋白H2A进行泛素化修饰（H2AK119ub1），这在体细胞中兼性异染色质形成的起始过程中发挥关键作用。在此，我们评估了精子来源的H2AK119ub1对胚胎发育的作用。在非洲爪蟾中，我们发现H2AK119ub1在精子发生过程中以及早期胚胎发育阶段均存在，这突出了其在从精子到胚胎的表观遗传信息传递中发挥作用的可能性。在将精子注入卵子之前，用H2AK119ub1去泛素化酶USP21对精子进行体外处理，会导致与基因上调相关的发育缺陷。精子H2AK119ub1编辑会破坏卵子因子介导的父本染色质重塑过程。它会导致基因组重复元件上而非CpG岛上H2AK119ub1在复制后积累。由精子表观基因组编辑引发的复制后H2AK119ub1分布的这种变化，导致在源自经USP21处理的精子的胚胎中，基因失调，H2AK119ub1缺失。我们得出结论，精子来源的H2AK119ub1指导卵子因子介导的父本染色质表观遗传重塑，是胚胎发育所必需的。
