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Pré-Publication, Document De Travail Année : 2021

TRIM28-dependent SUMOylation protects the adult ovary from the male pathway

Moïra Rossitto
  • Fonction : Auteur
Stephanie Déjardin
  • Fonction : Auteur
Chris M Rands
  • Fonction : Auteur
Stephanie Le Gras
Roberta Migale
  • Fonction : Auteur
Mahmoud-Reza Rafiee
  • Fonction : Auteur
Yasmine Neirijnck
Alain Pruvost
Anvi Laetitia Nguyen
Guillaume Bossis
Florence Cammas
  • Fonction : Auteur
Lionel Le Gallic
  • Fonction : Auteur
Dagmar Wilhelm
Robin Lovell-Badge
  • Fonction : Auteur
Brigitte Boizet-Bonhoure
Serge Nef

Résumé

Summary Gonadal sexual fate in mammals is determined during embryonic development and must be actively maintained in adulthood. Therefore, gonadal sex-specific transcription factors are required to prevent transdifferentiation of gonadal somatic cells to the other sexual fate. Mouse genetic experiments have shown that oestrogen receptor signalling and the transcription factor FOXL2 protect ovarian granulosa cells from transdifferentiation into Sertoli cells, their testicular counterpart. However, the mechanism underlying this protective mechanism is unknown. Here, we show that one post-translational modification (i.e. SUMOylation catalysed by TRIM28) is sufficient to prevent female-to-male sex reversal of the mouse ovary after birth. We found that upon loss of TRIM28 SUMO-E3 ligase activity, ovarian granulosa cells transdifferentiate to Sertoli cells through an intermediate cell type different from gonadal embryonic progenitors. TRIM28 binds to chromatin close to the critical transcription factor FOXL2 to maintain the female pathway through SUMOylation of specific chromatin regions. Therefore, FOXL2 signalling might maintain the adult ovary cell fate via TRIM28-dependent SUMOylation. Improper SUMOylation of chromatin regions in granulosa cells might lead to female reproductive disorders and infertility, the incidence of which is currently increasing.

Domaines

Biologie animale
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Dates et versions

hal-03436837 , version 1 (19-11-2021)

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Moïra Rossitto, Stephanie Déjardin, Chris M Rands, Stephanie Le Gras, Roberta Migale, et al.. TRIM28-dependent SUMOylation protects the adult ovary from the male pathway. 2021. ⟨hal-03436837⟩

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