Paper alert! Loss of SUMOylation drives aberrant PRC1 clustering and 3D genome rewiring independent of H3K27me3

SUMOylation is known to modulate PRC1 clustering, but its precise impact on condensates and 3D genome architecture remains unclear. Here we show that depleting SUMO in Drosophila wing discs enlarges PRC1 condensates and reduces internal mobility. Biophysical modeling suggests that these larger condensates result from an increase in PRC1 self-interactions when SUMO is depleted. Interestingly, this reorganization occurs without global loss of the H3K27me3 repressive mark, while Hi-C reveals widespread rewiring of TAD interactions. PRC1-bound TADs lose long-range contacts between them while gaining ectopic interactions with active TADs. These 3D rearrangements correlate with gene misregulation independently of H3K27me3. Overall, these results establish SUMOylation as a critical regulator of PRC1 condensates, showing that post-translational modifications can modulate PRC1 condensates, 3D genome architecture, and gene transcription.