Loss of SUMOylation drives aberrant PRC1 clustering and 3D genome rewiring independent of H3K27me3
Year: 2026
Type: article
Abstract: Polycomb repressive complex 1 (PRC1) forms nuclear condensates that organize target chromatin domains. SUMOylation modulates PRC1 clustering, but its impact on condensate properties and 3D genome architecture remains unclear. Here, we show that depletion of small ubiquitin-like modifier (SUMO) in Drosophila wing imaginal discs transforms PRC1 condensates into large structures with reduced molecular dynamics. Biophysical modeling suggests that the changes in PRC1 self-interactions are responsible for the formation of large PRC1 condensates when SUMO is depleted. Interestingly, 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. These topological shifts correlate with gene misregulation independently of changes in Polycomb histone modifications. Our results establish SUMOylation as a critical regulator of PRC1 condensates, demonstrating that post-translational control of biomolecular condensation modulates 3D genome architecture and transcriptional output through mechanisms separable from histone mark deposition.
Source: Nucleic Acids Research
DOI: 10.1093/nar/gkag851
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,992
Funders: Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Fondation pour la Recherche Médicale, Fondation ARC pour la Recherche sur le Cancer, Ligue Contre le Cancer, Centre National de la Recherche Scientifique, Université de Montpellier, Région Occitanie Pyrénées-Méditerranée, École Normale Supérieure de Lyon, Laboratoire d'Excellence EpiGenMed, H2020 European Research Council
Awards: G1190173965, Role of Rad51 filament structure and dynamics in homology search in living cells, Optogenetic probing of the 4D genome, Understanding how condensin folds chromatinized genomes into loops, Chromatin control of sperm nuclear compaction and shaping, Pilotage et gouvernance du programme Cell ID, Accessing individual Cell Identity in their native spatial context: The revolution of single cell and spatially resolved multi-omics., Training and career development & Innovation, G6299852252, G6372570281, LivChrom: The Living Chromatin framework to investigate the functional compartmentalization of the genome, Data Integration and Medical Applications, dedicated experimental systems
OpenAlex ID: W7128529819