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Scientific article
Open access
English

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

Published inNature communications, vol. 13, no. 1, 4412
Publication date2022-07-29
First online date2022-07-29
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.

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Keywords
  • Animals
  • Female
  • Male
  • Mammals / metabolism
  • Mice
  • Ovary / metabolism
  • Sertoli Cells / metabolism
  • Sumoylation
  • Testis / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Tripartite Motif-Containing Protein 28 / genetics
  • Tripartite Motif-Containing Protein 28 / metabolism
Citation (ISO format)
ROSSITTO, Moïra et al. TRIM28-dependent SUMOylation protects the adult ovary from activation of the testicular pathway. In: Nature communications, 2022, vol. 13, n° 1, p. 4412. doi: 10.1038/s41467-022-32061-1
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Identifiers
ISSN of the journal2041-1723
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Creation09/13/2022 1:09:00 PM
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Update time03/16/2023 7:32:58 AM
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