Dispersal of PRC1 condensates disrupts polycomb chromatin domains and loops

Iain Williamson, Shelagh Boyle, Graeme R Grimes, Elias Friman, Wendy A Bickmore*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Polycomb-repressive complex 1 (PRC1) strongly influences 3D genome organization,
47 mediating local chromatin compaction and clustering of target loci. Several PRC1 subunits
48 have the capacity to form biomolecular condensates through liquid-liquid phase separation in
49 vitro and when tagged and over-expressed in cells. Here, we use 1,6-hexandiol, which can
50 disrupt liquid-like condensates, to examine the role of endogenous PRC1 biomolecular
51 condensates on local and chromosome-wide clustering of PRC1-bound loci. Using imaging
52 and chromatin immunoprecipitation, we show that PRC1-mediated chromatin compaction
53 and clustering of targeted genomic loci – at different length scales – can be reversibly
54 disrupted by the addition and subsequent removal of 1,6-hexandiol to mouse embryonic stem
55 cells. Decompaction and dispersal of polycomb domains and clusters cannot be solely
56 attributable to reduced PRC1 occupancy detected by chromatin immunoprecipitation
57 following 1,6-hexandiol treatment as the addition of 2,5-hexandiol has similar effects on
58 binding despite this alcohol not perturbing PRC1-mediated 3D clustering, at least at the sub59 megabase and megabase scales. These results suggest that weak hydrophobic interactions
60 between PRC1 molecules may have a role in polycomb-mediated genome organization.
Original languageEnglish
JournalLife Science Alliance
Volume6
Issue number10
DOIs
Publication statusPublished - 24 Jul 2023

Keywords / Materials (for Non-textual outputs)

  • embryonic stem cells
  • biomolecular condensates
  • chromatin condensation
  • hexandiol
  • liquid-liquid phase separation
  • nuclear organization

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