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

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. Overall design: As the Trim28 cKO phenotype was similar to that of mice after Foxl2 deletion in adult ovarian follicles (Uhlenhaut et al, Cell 2009,139, 1130-42), we asked whether these two proteins co-regulated common target genes in the ovary. We performed TRIM28 and FOXL2 chromatin immunoprecipitation (ChIP) followed by next generation sequencing (ChIP-seq) in 8-weeks ovaries to gain a global view of TRIM28 and FOXL2 co-localization genome-wide.