BAP1 and UTX are dispensable for transcription-driven Polycomb erasure but essential for enhancer establishment.

Polycomb group (PcG) proteins safeguard cell identity by maintaining target genes in a transcriptionally repressed state through depositing two histone marks, H2A lysine-119 ubiquitination (H2AK119ub1) and H3 lysine-27 trimethylation (H3K27me3). BAP1 and UTX are thought to erase these marks during transcription activation, but their exact roles remain unclear. Here, we observe a rapid loss of H2AK119ub1, followed by a reduction in H3K27me3 levels at promoters on transcription induction, coinciding with a swift dissociation of Polycomb repressive complexes (PRCs). With an acute degradation system, we show that neither BAP1 nor UTX is required for transcription activation or the dissolution of Polycomb group repressive marks, though BAP1 depletion leads to elevated steady-state H2AK119ub1 levels. Furthermore, while UTX regulates enhancer activation independently of its demethylase activity, BAP1 contributes to this process through a dual role: its scaffolding function supports MLL4 occupancy at nascent enhancers, whereas its catalytic activity restricts H2AK119ub1 accumulation that would otherwise impede enhancer maturation. Together, these findings establish that BAP1 and UTX are dispensable for transcription-driven erasure of Polycomb marks but are required for enhancer establishment, with BAP1 acting through coordinated scaffolding and catalytic mechanisms.