Methylation mimic mutations of progesterone receptor AF1 impair gene-specific regulation through stabilized chromatin interactions
ChIP-seq analysis was conducted to determine the genome-wide binding profiles of PRB, PRB-FFF, and PRB-QQQ cell lines following R5020 treatment compared to vehicle (ETOH). We propose a tripartite model in which transient and calibrated interactions among AF1, AF2, and coregulators are essential for productive enhancer function and dynamic cycling of the transcription complex. We hypothesize that the PRB-FFF mutation leads to more stable interactions, resulting in prolonged enhancer occupancy and a slower transcription rate.