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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE166385 | GEO | 2022/05/24

REPOSITORIES: GEO

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

Project description: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.

| S-EPMC9338040 | biostudies-literature

TRIM28-dependent SUMOylation protects the adult ovary from the male pathway (RNA-Seq)

2022-05-24 | GSE166382 | GEO

TRIM28-dependent SUMOylation protects the adult ovary from the male pathway (ChIP-Seq 2)

Project description:We study the role of the protein Trim28 in the maintenance of sexual identity of the adult ovary. With the help of conditional knock out (cKO) of Trim28 using the Nr5a1:Cre, we observed that deletion of the Trim28 gene in granulosa cells of the adult ovary induces their transdifferentiation into Sertoli cells, the supporting cell lineage of the testicular seminiferous tubules. FOXL2 expression has disappeared and follicles were completely remodeled into tubular structures with cells that expressed the Sertoli cell markers SOX8, SOX9 and DMRT1. Histological analysis confirmed the progressive reorganization of ovarian follicles into tubular structures and the and the transdifferentiation of granulosa cells by cells with a Sertoli cell morphology. TRIM28 acts as a SUMO-E3 ligase by interacting with the SUMO-E2 conjugating enzyme UBC9 (encoded by the Ube2i gene) via the Plant homeodomain (PHD), and can self-SUMOylate. To study in vivo the role of TRIM28-dependent SUMOylation, we generated a point mutation in exon 13 of mouse Trim28 within the PHD domain of the TRIM28 protein (C651F) that abrogates its SUMO-E3 ligase activity. We generated Trim28Phd/cKO mice (termed PHD mutant). Like in cKO ovaries, FOXL2 expression was undetectable, whereas we observed expression of the Sertoli cell markers SOX9, SOX8 and DMRT1 within structures organized in pseudo-tubules in PHD ovaries. Our results indicate that maintenance of the female pathway in the adult ovary depends on the E3-SUMO ligase activity of TRIM28.

2022-05-24 | GSE166384 | GEO

TRIM28-dependent SUMOylation protects the adult ovary from the male pathway (ChIP-Seq 1)

2022-05-24 | GSE166383 | GEO

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

Project description:TRIM28-dependent SUMOylation protects the adult ovary from the male pathway

| PRJNA700643 | ENA

TRIM28-dependent SUMOylation protects the adult ovary from the male pathway (RNA-Seq)

Project description:TRIM28-dependent SUMOylation protects the adult ovary from the male pathway (RNA-Seq)

| PRJNA700646 | ENA

TRIM28-dependent SUMOylation protects the adult ovary from the male pathway (ChIP-Seq 2)

Project description:TRIM28-dependent SUMOylation protects the adult ovary from the male pathway (ChIP-Seq 2)

| PRJNA700645 | ENA

TRIM28-dependent SUMOylation protects the adult ovary from the male pathway (ChIP-Seq 1)

Project description:TRIM28-dependent SUMOylation protects the adult ovary from the male pathway (ChIP-Seq 1)

| PRJNA700648 | ENA

PRC2 controls adult neuron identity and protects neurons against neurodegeneration

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-07-29 | E-GEOD-84245 | biostudies-arrayexpress

TRIM28 protects TRIM24 from SPOP-mediated degradation and promotes prostate cancer progression

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-10-05 | GSE108146 | GEO

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