Maternal PRDM10 activates essential genes for oocyte-to-embryo transition

Abstract 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 fert...

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Main Authors: Michelle K. Y. Seah, Brenda Y. Han, Yan Huang, Louise J. H. Rasmussen, Andrina J. Stäubli, Judith Bello-Rodríguez, Andrew Chi-Ho Chan, Maxime Gasnier, Heike Wollmann, Ernesto Guccione, Daniel M. Messerschmidt
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-56991-8
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author Michelle K. Y. Seah
Brenda Y. Han
Yan Huang
Louise J. H. Rasmussen
Andrina J. Stäubli
Judith Bello-Rodríguez
Andrew Chi-Ho Chan
Maxime Gasnier
Heike Wollmann
Ernesto Guccione
Daniel M. Messerschmidt
author_facet Michelle K. Y. Seah
Brenda Y. Han
Yan Huang
Louise J. H. Rasmussen
Andrina J. Stäubli
Judith Bello-Rodríguez
Andrew Chi-Ho Chan
Maxime Gasnier
Heike Wollmann
Ernesto Guccione
Daniel M. Messerschmidt
author_sort Michelle K. Y. Seah
collection DOAJ
description Abstract 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.
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spelling doaj-art-3e44a96d123e4fc193f7ef0174c05c8d2025-08-20T02:01:30ZengNature PortfolioNature Communications2041-17232025-02-0116111310.1038/s41467-025-56991-8Maternal PRDM10 activates essential genes for oocyte-to-embryo transitionMichelle K. Y. Seah0Brenda Y. Han1Yan Huang2Louise J. H. Rasmussen3Andrina J. Stäubli4Judith Bello-Rodríguez5Andrew Chi-Ho Chan6Maxime Gasnier7Heike Wollmann8Ernesto Guccione9Daniel M. Messerschmidt10Institute of Molecular and Cell Biology (IMCB), Agency for Science Technology and Research (A*STAR)Institute of Molecular and Cell Biology (IMCB), Agency for Science Technology and Research (A*STAR)Institute for Cellular and Molecular Medicine, University of CopenhagenInstitute for Cellular and Molecular Medicine, University of CopenhagenInstitute for Cellular and Molecular Medicine, University of CopenhagenDNRF Center for Chromosome Stability, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of CopenhagenDNRF Center for Chromosome Stability, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of CopenhagenInstitute of Molecular and Cell Biology (IMCB), Agency for Science Technology and Research (A*STAR)Novo Nordisk Foundation Center for Stem Cell Medicine, reNEW, University of CopenhagenCenter for OncoGenomics and Innovative Therapeutics (COGIT) Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount SinaiInstitute of Molecular and Cell Biology (IMCB), Agency for Science Technology and Research (A*STAR)Abstract 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.https://doi.org/10.1038/s41467-025-56991-8
spellingShingle Michelle K. Y. Seah
Brenda Y. Han
Yan Huang
Louise J. H. Rasmussen
Andrina J. Stäubli
Judith Bello-Rodríguez
Andrew Chi-Ho Chan
Maxime Gasnier
Heike Wollmann
Ernesto Guccione
Daniel M. Messerschmidt
Maternal PRDM10 activates essential genes for oocyte-to-embryo transition
Nature Communications
title Maternal PRDM10 activates essential genes for oocyte-to-embryo transition
title_full Maternal PRDM10 activates essential genes for oocyte-to-embryo transition
title_fullStr Maternal PRDM10 activates essential genes for oocyte-to-embryo transition
title_full_unstemmed Maternal PRDM10 activates essential genes for oocyte-to-embryo transition
title_short Maternal PRDM10 activates essential genes for oocyte-to-embryo transition
title_sort maternal prdm10 activates essential genes for oocyte to embryo transition
url https://doi.org/10.1038/s41467-025-56991-8
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