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

Author

Listed:
  • Moïra Rossitto

    (CNRS UMR9002 University of Montpellier
    Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286)

  • 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)

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.

Suggested Citation

  • Moïra Rossitto & Stephanie Déjardin & Chris M. Rands & Stephanie Gras & Roberta Migale & Mahmoud-Reza Rafiee & Yasmine Neirijnck & Alain Pruvost & Anvi Laetitia Nguyen & Guillaume Bossis & Florence Ca, 2022. "TRIM28-dependent SUMOylation protects the adult ovary from activation of the testicular pathway," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32061-1
    DOI: 10.1038/s41467-022-32061-1
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    References listed on IDEAS

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    1. Damien Dufour & Typhanie Dumontet & Isabelle Sahut-Barnola & Aude Carusi & Méline Onzon & Eric Pussard & James Jr Wilmouth & Julie Olabe & Cécily Lucas & Adrien Levasseur & Christelle Damon-Soubeyrand, 2022. "Loss of SUMO-specific protease 2 causes isolated glucocorticoid deficiency by blocking adrenal cortex zonal transdifferentiation in mice," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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