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Nat Genet. 2017 Feb;49(2):213-222. doi: 10.1038/ng.3734. Epub 2016 Dec 12.

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

Author information

1
Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
2
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
3
Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
4
Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, California, USA.

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.

PMID:
27941796
PMCID:
PMC5285326
DOI:
10.1038/ng.3734
[Indexed for MEDLINE]
Free PMC Article

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