Scientific article

mSWI/SNF promotes Polycomb repression both directly and through genome-wide redistribution

Published inNature Structural & Molecular Biology, vol. 28, no. 6, p. 501-511
Publication date2021

The mammalian SWI/SNF complex, or BAF complex, has a conserved and direct role in antagonizing Polycomb-mediated repression. Yet, BAF also promotes repression by Polycomb in stem cells and cancer. How BAF both antagonizes and promotes Polycomb-mediated repression remains unknown. Here, we utilize targeted protein degradation to dissect the BAF-Polycomb axis in mouse embryonic stem cells on short timescales. We report that rapid BAF depletion redistributes Polycomb repressive complexes PRC1 and PRC2 from highly occupied domains, like Hox clusters, to weakly occupied sites normally opposed by BAF. Polycomb redistribution from highly repressed domains results in their decompaction, gain of active epigenomic features and transcriptional derepression. Surprisingly, through dose-dependent degradation of PRC1 and PRC2, we identify a conventional role for BAF in Polycomb-mediated repression, in addition to global Polycomb redistribution. These findings provide new mechanistic insight into the highly dynamic state of the Polycomb-Trithorax axis.

  • Animals
  • CRISPR-Cas Systems
  • Cells
  • Cultured
  • Chromatin Assembly and Disassembly/genetics/physiology
  • DNA Helicases/genetics/metabolism
  • DNA-Binding Proteins/physiology
  • Embryonic Stem Cells/metabolism
  • Epigenesis
  • Genetic
  • Epigenetic Repression/genetics/physiology
  • Gene Editing
  • Gene Expression Regulation/genetics/physiology
  • Genes
  • Homeobox
  • Genome
  • HEK293 Cells
  • Homeodomain Proteins/genetics/metabolism
  • Humans
  • Loss of Function Mutation
  • Mice
  • Multiprotein Complexes/physiology
  • Nuclear Proteins/genetics/metabolism
  • Polycomb-Group Proteins/physiology
  • Proteolysis
  • Recombinant Fusion Proteins/metabolism
  • Transcription Factors/genetics/metabolism/physiology
Citation (ISO format)
WEBER, Christopher M et al. mSWI/SNF promotes Polycomb repression both directly and through genome-wide redistribution. In: Nature Structural & Molecular Biology, 2021, vol. 28, n° 6, p. 501–511. doi: 10.1038/s41594-021-00604-7
Main files (1)
Article (Published version)
ISSN of the journal1545-9985

Technical informations

Creation09/01/2021 4:29:00 PM
First validation09/01/2021 4:29:00 PM
Update time03/16/2023 1:14:43 AM
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