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Scientific article
English

Dynamics of BAF-Polycomb complex opposition on heterochromatin in normal and oncogenic states

Published inNature Genetics, vol. 49, no. 2, p. 213-222
Publication date2017
Abstract

The opposition between Polycomb repressive complexes (PRCs) and BAF (mSWI/SNF) complexes has a critical role in both development and disease. Mutations in the genes encoding BAF subunits contribute to more than 20% of human malignancies, yet the underlying mechanisms remain unclear, owing largely to a lack of assays to assess BAF function in living cells. To address this, we have developed a widely applicable recruitment assay system through which we find that BAF opposes PRC by rapid, ATP-dependent eviction, leading to the formation of accessible chromatin. The reversal of this process results in reassembly of facultative heterochromatin. Surprisingly, BAF-mediated PRC eviction occurs in the absence of RNA polymerase II (Pol II) occupancy, transcription, and replication. Further, we find that tumor-suppressor and oncogenic mutant BAF complexes have different effects on PRC eviction. The results of these studies define a mechanistic sequence underlying the resolution and formation of facultative heterochromatin, and they demonstrate that BAF opposes PRC on a minute-by-minute basis to provide epigenetic plasticity.

Keywords
  • Carcinogenesis/genetics
  • Chromatin/genetics
  • DNA Replication/genetics
  • DNA-Binding Proteins/genetics
  • Epigenesis
  • Genetic/genetics
  • Heterochromatin/genetics
  • Humans
  • Mutation/genetics
  • Nuclear Proteins/genetics
  • Polycomb-Group Proteins/genetics
  • RNA Polymerase II/genetics
  • Transcription
  • Genetic/genetics
Affiliation Not a UNIGE publication
Citation (ISO format)
KADOCH, Cigall et al. Dynamics of BAF-Polycomb complex opposition on heterochromatin in normal and oncogenic states. In: Nature Genetics, 2017, vol. 49, n° 2, p. 213–222. doi: 10.1038/ng.3734
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ISSN of the journal1061-4036
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