The SS18-SSX Fusion Oncoprotein Hijacks BAF Complex Targeting and Function to Drive Synovial Sarcoma.
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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. |
Year of Publication | 2018
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Journal | Cancer Cell
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Volume | 33
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Issue | 6
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Pages | 1128-1141.e7
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Date Published | 2018 06 11
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ISSN | 1878-3686
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DOI | 10.1016/j.ccell.2018.05.002
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PubMed ID | 29861296
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PubMed Central ID | PMC6791822
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Grant list | DP2 CA195762 / CA / NCI NIH HHS / United States
R01 CA237241 / CA / NCI NIH HHS / United States
T32 GM095450 / GM / NIGMS NIH HHS / United States
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