TRIM28-dependent SUMOylation protects the adult ovary from activation of the testicular pathway
Author(s)
Type
Journal Article
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<jats:italic>Trim28</jats:italic>, 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 Issued
2022-07-29
Date Acceptance
2022-07-17
Citation
Nature Communications, 2022, 13
ISSN
2041-1723
Publisher
Nature Portfolio
Start Page
4412
Journal / Book Title
Nature Communications
Volume
13
Issue
1
Copyright Statement
© The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/35906245
PII: 10.1038/s41467-022-32061-1
Subjects
Animals
Female
Male
Mammals
Mice
Ovary
Sertoli Cells
Sumoylation
Testis
Transcription Factors
Tripartite Motif-Containing Protein 28
Publication Status
Published
Coverage Spatial
England
Article Number
4412
Date Publish Online
2022-07-29