Published December 31, 2026 | Version v2
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Polycomb-mediated gene repression by a heterologous phase separating intrinsically disordered region

Authors/Creators

  • 1. ROR icon Harvard Medical School
  • 2. ROR icon Massachusetts General Hospital

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Data manager:

  • 1. ROR icon Harvard Medical School
  • 2. ROR icon Massachusetts General Hospital

Description

This repository holds the bioinformatics pipeline for processing CUT&RUN and RNA-Seq data to reproduce the analysis of the paper mentioned in the title.

Abstract

Polycomb Group (PcG) proteins play an essential role in development through the maintenance of repressed chromatin states. Proper axial patterning in mice, condensate formation in cells, and nucleosome compaction in vitro, are driven by the Intrinsically Disordered Region (IDR) of CBX2, a subunit of canonical Polycomb Repressive Complex 1 (cPRC1). To investigate the significance of phase separation activity, we fused a condensation-deficient CBX2 IDR mutant to heterologous IDRs. The FUS IDR functionally rescued the CBX2 mutant in a neuronal lineage by inducing Polycomb body formation and suppressing neurite elongation. The fusion construct binds to similar genomic targets as wildtype cPRC1 and represses transcription. Orthogonal phase separation activity is sufficient to rescue CBX2 function, demonstrating the central role of phase separation in Polycomb-mediated epigenetic regulation.

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Dates

Created
2026-03-18
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