| Title | The SS18-SSX Fusion Oncoprotein Hijacks BAF Complex Targeting and Function to Drive Synovial Sarcoma. |
| Publication Type | Journal Article |
| Year of Publication | 2018 |
| Authors | McBride MJ, Pulice JL, Beird HC, Ingram DR, D'Avino AR, Shern JF, Charville GW, Hornick JL, Nakayama RT, Garcia-Rivera EM, Araujo DM, Wang W-L, Tsai J-W, Yeagley M, Wagner AJ, P Futreal A, Khan J, Lazar AJ, Kadoch C |
| Journal | Cancer Cell |
| Volume | 33 |
| Issue | 6 |
| Pagination | 1128-1141.e7 |
| Date Published | 2018 06 11 |
| ISSN | 1878-3686 |
| Keywords | Cell Line, Tumor, Chromatin, Enhancer Elements, Genetic, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, HEK293 Cells, Humans, Oncogene Proteins, Fusion, Sarcoma, Synovial, SMARCB1 Protein, Whole Exome Sequencing |
| 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. |
| DOI | 10.1016/j.ccell.2018.05.002 |
| Alternate Journal | Cancer Cell |
| PubMed ID | 29861296 |
| PubMed Central ID | PMC6791822 |
| 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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