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

作者：Kadoch Cigall; Williams Robert T; Calarco Joseph P; Miller Erik L; Weber Christopher M; Braun Simon M G; Pulice John L; Chory Emma J; Crabtree Gerald R

来源：Nature Genetics, 2017, 49(2): 213-222.

DOI：10.1038/ng.3734

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.

• 出版日期2017-2