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Loss of SUMOylation drives aberrant PRC1 clustering and 3D genome rewiring independent of H3K27me3.
Nucleic Acids Res, 54(17).
Polycomb repressive complex 1 (PRC1) forms nuclear condensates that organizetarget chromatin domains. SUMOylation modulates PRC1 clustering, but its impacton condensate properties and 3D genome architecture remains unclear. Here, weshow that depletion of small ubiquitin-like modifier (SUMO) in Drosophila wingimaginal discs transforms PRC1 condensates into large structures with reducedmolecular dynamics. Biophysical modeling suggests that the changes in PRC1self-interactions are responsible for the formation of large PRC1 condensateswhen SUMO is depleted. Interestingly, this biophysical reorganization occurswithout global loss of the H3K27me3 mark. Instead, Hi-C reveals widespreadrewiring of topologically associating domain (TAD) interactions. PRC1-bound TADslose specific long-range contacts with each other while gaining ectopicinteractions with active chromatin. These topological shifts correlate with genemisregulation independently of changes in Polycomb histone modifications. Ourresults establish SUMOylation as a critical regulator of PRC1 condensates,demonstrating that post-translational control of biomolecular condensationmodulates 3D genome architecture and transcriptional output through mechanismsseparable from histone mark deposition.
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