Principles of assembly and regulation of condensates of Polycomb repressive complex 1 through phase separation
Kyle Brown,
Pin Yu Chew,
Steven Ingersoll,
Jorge R. Espinosa,
Anne Aguirre,
Axel Espinoza,
Joey Wen,
Kalkidan Astatike,
Tatiana G. Kutateladze,
Rosana Collepardo-Guevara,
Xiaojun Ren
Affiliations
Kyle Brown
Department of Chemistry, University of Colorado Denver, Denver, CO 80217-3364, USA
Pin Yu Chew
Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK
Steven Ingersoll
Department of Chemistry, University of Colorado Denver, Denver, CO 80217-3364, USA
Jorge R. Espinosa
Department of Physics, University of Cambridge, Cambridge CB3 0HE, UK
Anne Aguirre
Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK
Axel Espinoza
Department of Chemistry, University of Colorado Denver, Denver, CO 80217-3364, USA
Joey Wen
Department of Chemistry, University of Colorado Denver, Denver, CO 80217-3364, USA
Kalkidan Astatike
Department of Chemistry, University of Colorado Denver, Denver, CO 80217-3364, USA
Tatiana G. Kutateladze
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA
Rosana Collepardo-Guevara
Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK; Department of Physics, University of Cambridge, Cambridge CB3 0HE, UK; Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK; Corresponding author
Xiaojun Ren
Department of Chemistry, University of Colorado Denver, Denver, CO 80217-3364, USA; Department of Integrative Biology, University of Colorado Denver, Denver, CO 80217-3364, USA; Corresponding author
Summary: Polycomb repressive complex 1 (PRC1) undergoes phase separation to form Polycomb condensates that are multi-component hubs for silencing Polycomb target genes. In this study, we demonstrate that formation and regulation of PRC1 condensates are consistent with the scaffold-client model, where the Chromobox 2 (CBX2) protein behaves as the scaffold while the other PRC1 proteins are clients. Such clients induce a re-entrant phase transition of CBX2 condensates. The composition of the multi-component PRC1 condensates (1) determines the dynamic properties of the scaffold protein; (2) selectively promotes the formation of CBX4-PRC1 condensates while dissolving condensates of CBX6-, CBX7-, and CBX8-PRC1; and (3) controls the enrichment of CBX4-, CBX7-, and CBX8-PRC1 in CBX2-PRC1 condensates and the exclusion of CBX6-PRC1 from CBX2-PRC1 condensates. Our findings uncover how multi-component PRC1 condensates are assembled via an intricate scaffold-client mechanism whereby the properties of the PRC1 condensates are sensitively regulated by its composition and stoichiometry.
