Signal Preprint identifies TRIM28 as a stabiliser of ovarian cell identity

Summary

A study reports the mechanism through which the protein TRIM28 preserves the identity of ovarian cells. Granulosa cells must resist converting into a testicular cell type called Sertoli cells throughout life, yet the epigenetic mechanism behind this protection had remained unclear. Because TRIM28 can both build repressive heterochromatin and activate transcription, the researchers combined several epigenomic profiling methods to tease apart how much each function contributes. They found that only a small portion of the regions TRIM28 occupies carried the repressive heterochromatin mark, and removing TRIM28 had limited transcriptional impact that was mostly confined to repetitive DNA elements. In contrast, losing TRIM28 sharply reduced chromatin accessibility and active chromatin marks at sites enriched for ovary-specific transcription factors, which TRIM28 was frequently found occupying together with those factors. The team concludes that TRIM28 functions primarily as an organizer that stabilizes lineage-specific transcription factor hubs, rather than through heterochromatin formation, to preserve granulosa cell identity.