Maternal PRDM10 activates essential genes for oocyte-to-embryo transition
PR/SET domain-containing (PRDM) proteins are metazoan-specific transcriptional regulators that play diverse roles in mammalian development and disease. Several members such as PRDM1, PRDM14 and PRDM9, have been implicated in germ cell specification and homoeostasis and are essential to fertility-related processes. Others, such as PRDM14, PRDM15 and PRDM10 play a role in early embryogenesis and embryonic stem cell maintenance. Here, we describe the first PRDM family member with a maternal effect. Absence of maternal Prdm10 results in catastrophic failure of oocyte-to-embryo transition and complete arrest at the 2-cell stage. We describe multiple defects in oocytes, zygotes and 2-cell stage embryos relating to the failure to accumulate PRDM10 target gene transcripts in the egg. Transcriptomic analysis and integration of genome-wide chromatin-binding data reveals new and essential PRDM10 targets, including the cytoskeletal protein encoding gene Septin11. We demonstrate that the failure to express maternal Septin11, in the absence of maternal PRDM10, disrupts Septin-complex assembly at the polar body extrusion site in MII oocytes. Our study sheds light into the essentiality of maternal PRDM10, the requirement of the maternal Septin-complex and the likely evolutionary conservation of this regulatory axis in human female germ cells.
Authors
- A Staübli
- Andrew C. Chan (ORCID: https://orcid.org/0000-0001-7523-6139)
- Daniel M. Messerschmidt (ORCID: https://orcid.org/0000-0003-2022-4696)
- Yuyuan Han (ORCID: https://orcid.org/0000-0002-3212-875X)
- Yan Huang (ORCID: https://orcid.org/0000-0003-4704-4767)
- Maxime Gasnier (ORCID: https://orcid.org/0009-0005-9988-3847)
- Ernesto Guccione (ORCID: https://orcid.org/0000-0001-7764-5307)
- Michelle K. Y. Seah (ORCID: https://orcid.org/0000-0003-1490-752X)
- L. Rasmussen (ORCID: https://orcid.org/0000-0003-1277-3193)
- Heike Wollmann (ORCID: https://orcid.org/0000-0002-7666-8432)
- Judith Bello-Rodríguez (ORCID: https://orcid.org/0000-0001-8418-3366)
Institutions
- Agency for Science, Technology and Research (SG)
- University of Copenhagen (DK)
- National University of Singapore (SG)
- Novo Nordisk Foundation (DK)
- Institute of Molecular and Cell Biology (SG)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-02-24
- DOI
- https://doi.org/10.1038/s41467-025-56991-8
- Citations
- 3
- Primary Topic
- Reproductive Biology and Fertility
- Type
- article
- Field-Weighted Citation Impact
- 5.64
Funders
- Icahn School of Medicine at Mount Sinai
- Georgia Clinical and Translational Science Alliance
- National Research Foundation
- Danmarks Grundforskningsfond
- Bundesministerium für Bildung und Forschung
- Albert-Ludwigs-Universität Freiburg
- Novo Nordisk
- Novo Nordisk Fonden
- German Network for Bioinformatics Infrastructure
- National Institutes of Health
- National Cancer Institute
- National Center for Advancing Translational Sciences
- Eunice Kennedy Shriver National Institute of Child Health and Human Development