Dynamics of BAF-Polycomb complex opposition on heterochromatin in normal and oncogenic states
| Autor: | Erik L. Miller, Simon M. G. Braun, Gerald R. Crabtree, Emma J. Chory, Cigall Kadoch, Robert T Williams, Joseph P Calarco, Christopher M. Weber, John L. Pulice |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
DNA Replication
0301 basic medicine DNA Replication/genetics Transcription Genetic Mutation/genetics Carcinogenesis Heterochromatin Polycomb-Group Proteins RNA polymerase II RNA Polymerase II/genetics DNA-binding protein Article Epigenesis Genetic 03 medical and health sciences Transcription (biology) Polycomb-Group Proteins/genetics Genetics Polycomb-group proteins Humans Epigenetics Genetic/genetics biology Chromatin/genetics DNA replication Nuclear Proteins Heterochromatin/genetics Chromatin DNA-Binding Proteins Nuclear Proteins/genetics 030104 developmental biology Mutation biology.protein RNA Polymerase II Carcinogenesis/genetics Transcription DNA-Binding Proteins/genetics Epigenesis |
| Zdroj: | Nature Genetics, Vol. 49, No 2 (2017) pp. 213-222 Nature genetics |
| ISSN: | 1061-4036 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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