Loss of SUMOylation drives aberrant PRC1 clustering and 3D genome rewiring independent of H3K27me3
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.
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BibTeX
@article{akilli2026loss,
title = {{Loss of SUMOylation drives aberrant PRC1 clustering and 3D genome rewiring independent of H3K27me3}},
author = {Nazli Akilli and Paul-Swann Puel and Marco Di Stefano and Fernando Muzzopappa and Lauriane Fritsch and Fabian Erdel and Daniel Jost and Thierry Cheutin and Giacomo Cavalli},
journal = {Nucleic Acids Research},
year = {2026},
month = sep,
doi = {10.1093/nar/gkag851},
url = {https://hal.umontpellier.fr/hal-05761104v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Loss of SUMOylation drives aberrant PRC1 clustering and 3D genome rewiring independent of H3K27me3
AU - Nazli Akilli
AU - Paul-Swann Puel
AU - Marco Di Stefano
AU - Fernando Muzzopappa
AU - Lauriane Fritsch
AU - Fabian Erdel
AU - Daniel Jost
AU - Thierry Cheutin
AU - Giacomo Cavalli
PY - 2026
DA - 2026/09/23
JO - Nucleic Acids Research
DO - 10.1093/nar/gkag851
UR - https://hal.umontpellier.fr/hal-05761104v1
AB - 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.
SN - 0305-1048
SN - 1362-4962
ER -