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

Cell Reports (Oct 2023)

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

Journal volume & issue: Vol. 42, no. 10
p. 113136

Abstract

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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.

CP: Molecular biology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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