Modularity of PRC1 composition and chromatin interaction define condensate properties.

Polycomb repressive complexes (PRCs) play a key role in gene repression and are indispensable for proper development. Canonical PRC1 forms condensates in vitro and in cells that are proposed to contribute to the maintenance of repression. However, how chromatin and the various subunits of PRC1 contribute to condensation is largely unexplored. Using a reconstitution approach and single-molecule imaging, we demonstrate that nucleosomal arrays and PRC1 act synergistically, reducing the critical concentration required for condensation by more than 20-fold. We find that the exact combination of PHC and CBX subunits determines condensate initiation, morphology, stability, and dynamics. Particularly, PHC2's polymerization activity influences condensate dynamics by promoting the formation of distinct domains that adhere to each other but do not coalesce. Live-cell imaging confirms CBX's role in condensate initiation and highlights PHC's importance for condensate stability. We propose that PRC1 composition can modulate condensate properties, providing crucial regulatory flexibility across developmental stages. [Display omitted] • Nucleosomal arrays and PRC1 act synergistically to form condensates • PRC1 pre-wetting of chromatin initiates switch-like transition to form condensates • Modularity of PRC1 complex composition fine-tunes condensate properties • PHC polymerization alters condensate properties forming distinct long-lived domains Through reconstitution and imaging, Niekamp et al. reveal that the Polycomb repressive complex 1 (PRC1) and chromatin act synergistically to form condensates. They show that specific combinations of PHC and CBX subunits determine condensate initiation, morphology, stability, and dynamics, which could provide important flexibility in regulatory functions across developmental stages. [ABSTRACT FROM AUTHOR]