TRIM28-dependent SUMOylation protects the adult ovary from activation of the testicular pathway

Moïra Rossitto, Stephanie Déjardin, Chris M. Rands, Stephanie Gras, Roberta Migale, Mahmoud-Reza Rafiee, Yasmine Neirijnck, Alain Pruvost, Anvi Laetitia Nguyen, Guillaume Bossis, Florence Cammas, Lionel Gallic, Dagmar Wilhelm, Robin Lovell-Badge, Brigitte Boizet-Bonhoure, Serge Nef and Francis Poulat ()
Additional contact information
Moïra Rossitto: CNRS UMR9002 University of Montpellier
Stephanie Déjardin: CNRS UMR9002 University of Montpellier
Chris M. Rands: University of Geneva CMU, lab E09.2750.B 1
Stephanie Gras: GenomEast platform, IGBMC, 1, rue Laurent Fries
Roberta Migale: The Francis Crick Institute
Mahmoud-Reza Rafiee: The Francis Crick Institute
Yasmine Neirijnck: University of Geneva CMU, lab E09.2750.B 1
Alain Pruvost: Université Paris Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SPI
Anvi Laetitia Nguyen: Université Paris Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SPI
Guillaume Bossis: University of Montpellier, CNRS
Florence Cammas: Institut de Recherche en Cancérologie de Montpellier, IRCM, INSERM U1194, Université de Montpellier, Institut régional du Cancer de Montpellier
Lionel Gallic: CNRS UMR9002 University of Montpellier
Dagmar Wilhelm: University of Melbourne
Robin Lovell-Badge: The Francis Crick Institute
Brigitte Boizet-Bonhoure: CNRS UMR9002 University of Montpellier
Serge Nef: University of Geneva CMU, lab E09.2750.B 1
Francis Poulat: CNRS UMR9002 University of Montpellier

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: Abstract Gonadal sexual fate in mammals is determined during embryonic development and must be actively maintained in adulthood. In the mouse ovary, oestrogen receptors and FOXL2 protect ovarian granulosa cells from transdifferentiation into Sertoli cells, their testicular counterpart. However, the mechanism underlying their protective effect is unknown. Here, we show that TRIM28 is required to prevent female-to-male sex reversal of the mouse ovary after birth. We found that upon loss of Trim28, ovarian granulosa cells transdifferentiate to Sertoli cells through an intermediate cell type, different from gonadal embryonic progenitors. TRIM28 is recruited on chromatin in the proximity of FOXL2 to maintain the ovarian pathway and to repress testicular-specific genes. The role of TRIM28 in ovarian maintenance depends on its E3-SUMO ligase activity that regulates the sex-specific SUMOylation profile of ovarian-specific genes. Our study identifies TRIM28 as a key factor in protecting the adult ovary from the testicular pathway.

Date: 2022
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DOI: 10.1038/s41467-022-32061-1

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