Polycomb erasers BAP1 and UTX are dispensable for rapid bivalent gene activation but essential for enhancer establishment [CUT&Tag]

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 upon transcription induction, coinciding with a swift dissociation of PRCs. With an acute degradation system, we show that BAP1 and UTX are dispensable for transcription activation or the dissolution of PcG repressive marks. Instead, they promote enhancer establishment during cell fate transition independent of their eraser enzymatic activity. Therefore, our study provides novel mechanistic insights that the dissolution of PcG-marks is transcription-dependent while UTX and BAP1 primarily function as bridging factors to construct enhancers, rather than as erasers of PcG memory.