Journal
NATURE GENETICS
Volume 49, Issue 2, Pages 213-222Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3734
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Funding
- NIH Director's New Innovator Award DP2 [1DP2CA195762-01]
- American Cancer Society Scholar Award [RSG-14-051-01-DMC]
- Pew Scholar Award
- A.P. Giannini Foundation
- Alex's Lemonade Stand Foundation (ALSF) Young Investigator Award
- NIH SARC Sarcoma SPORE Career Development and SPORE Project [5U54 CA168512-04]
- NIH grants [CA163915, NS046789]
- CIRM [RB4-05886]
- Howard Hughes Medical Institute
- SPARS
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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.
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