Identification of a p300–SP1–BRD4 Transcriptional Axis as a Key Driver of AR Hyperactivation in Polycystic Ovarian Syndrome

This study identifies a transcriptional axis involving p300, SP1, and BRD4 as a key driver of androgen receptor (AR) hyperactivation in polycystic ovarian syndrome (PCOS). Using mouse models and data from 15 women with PCOS, researchers found that p300 upregulation leads to increased AR expression and histone acetylation, contributing to ovarian fibrosis. Techniques like ATAC-seq and RNA-seq showed that p300 enhances AR expression by increasing chromatin accessibility and SP1 footprint dynamics at the AR promoter. Pharmacological inhibition and genetic deletion of p300 reduced AR activation and alleviated PCOS-like symptoms, suggesting that targeting the p300–SP1–BRD4 axis could be a promising therapeutic strategy for PCOS.