title: Dynamics of BAF-Polycomb complex opposition on heterochromatin in normal and oncogenic states.
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.
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.|Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Cigall
authors.identifier: http://orcid.org/0000-0002-4058-5985
authors.initials: C
authors.lastname: Kadoch
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Williams
authors.affiliation: Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.|Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Calarco
authors.affiliation: Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.|Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Erik L
authors.initials: EL
authors.lastname: Miller
authors.affiliation: Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.|Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Weber
authors.affiliation: Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.|Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Simon M G
authors.initials: SM
authors.lastname: Braun
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.|Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Pulice
authors.affiliation: Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.|Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Chory
authors.affiliation: Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.|Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Gerald R
authors.initials: GR
authors.lastname: Crabtree
mesh_terms: D063646:Carcinogenesis / Q000235:genetics*; D002843:Chromatin / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics; D006570:Heterochromatin / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D063146:Polycomb-Group Proteins / Q000235:genetics*; D012319:RNA Polymerase II / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: C501959:BANF1 protein, human; D002843:Chromatin; D004268:DNA-Binding Proteins; D006570:Heterochromatin; D009687:Nuclear Proteins; D063146:Polycomb-Group Proteins; D012319:RNA Polymerase II