Loss of SUMOylation drives aberrant PRC1 clustering and 3D genome rewiring independent of H3K27me3 [Hi-C]

SUMOylation modulates PRC1 clustering, but its impact on condensate properties and 3D genome architecture remains unclear. Here, we show that depletion of SUMO in Drosophila wing imaginal discs transforms PRC1 condensates into large structures with reduced molecular dynamics.

Strikingly, this biophysical reorganization occurs without global loss of the H3K27me3 mark. Instead, Hi-C reveals widespread rewiring of topologically associating domain (TAD) interactions. PRC1-bound TADs lose specific long-range contacts with each other while gaining ectopic interactions with active chromatin.