15 decembre 2022 à 11 h :

ROLE OF TRIM28 IN OVARIAN MAINTENANCE

Francis  POULAT –

Institute of Human Genetics, CNRS UMR9002, University of Monptellier, France

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.

Selected publications :

1. Rossitto M, Déjardin S, Rands CM, Le Gras S, Migale R, Rafiee MR, Neirijnck Y, Pruvost A, Nguyen AL, Bossis G, Cammas F, Le Gallic L, Wilhelm D, Lovell-Badge R, Boizet-Bonhoure B, Nef S, Poulat F. TRIM28-dependent SUMOylation protects the adult ovary from activation of the testicular pathway. Nat Commun. 2022 Jul 29;13(1):4412.
2. Poulat F. : Non-Coding Genome, Transcription Factors, and Sex Determination. Sex Dev. 2021;15(5-6):295-307
3. Gonen N, Futtner CR, Wood S, Garcia-Moreno SA, Salamone IM, Samson SC, Sekido R, Poulat F, Maatouk DM, Lovell-Badge R. Sex reversal following deletion of a single distal enhancer of Sox9. 2018 Jun 29;360(6396):1469-1473.
4. Rahmoun M, Lavery R, Laurent-Chaballier S, Bellora N, Philip GK, Rossitto M, Symon A, Pailhoux E, Cammas F, Chung J, Bagheri-Fam S, Murphy M, Bardwell V, Zarkower D, Boizet-Bonhoure B, Clair P, Harley VR, Poulat F: In mammalian foetal testes, SOX9 regulates expression of its target genes by binding to genomic regions with conserved signatures. Nucleic Acids Res. 2017 Jul 7;45(12):7191-7211.

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