| Literature DB >> 29861296 |
Matthew J McBride1, John L Pulice2, Hannah C Beird3, Davis R Ingram4, Andrew R D'Avino2, Jack F Shern5, Gregory W Charville6, Jason L Hornick7, Robert T Nakayama8, Enrique M Garcia-Rivera2, Dejka M Araujo9, Wei-Lien Wang4, Jen-Wei Tsai4, Michelle Yeagley9, Andrew J Wagner10, P Andrew Futreal3, Javed Khan5, Alexander J Lazar11, Cigall Kadoch12.
Abstract
Synovial sarcoma (SS) is defined by the hallmark SS18-SSX fusion oncoprotein, which renders BAF complexes aberrant in two manners: gain of SSX to the SS18 subunit and concomitant loss of BAF47 subunit assembly. Here we demonstrate that SS18-SSX globally hijacks BAF complexes on chromatin to activate an SS transcriptional signature that we define using primary tumors and cell lines. Specifically, SS18-SSX retargets BAF complexes from enhancers to broad polycomb domains to oppose PRC2-mediated repression and activate bivalent genes. Upon suppression of SS18-SSX, reassembly of BAF47 restores enhancer activation, but is not required for proliferative arrest. These results establish a global hijacking mechanism for SS18-SSX on chromatin, and define the distinct contributions of two concurrent BAF complex perturbations.Entities:
Keywords: ATP-dependent chromatin remodeling; SWI/SNF (BAF) complexes; bivalency; chromatin; enhancers; fusion oncoprotein; pediatric cancer; polycomb; synovial sarcoma
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Year: 2018 PMID： 29861296 PMCID： PMC6791822 DOI： 10.1016/j.ccell.2018.05.002
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743