Project name: The SS18-SSX fusion oncoprotein hijacks BAF complex targeting and function to drive synovial sarcoma [ChIP-Seq]

Description: 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 a SS transcriptional signature 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.Overall design: Synovial sarcoma cell lines (Aska, HSSY2, SYO1) were lentivirally infected with either an shControl or a shSSX vector, selected for 48 hours with puromycin, then grown for 5 days, at which point cells were harvested for ChIP-seq preparation. CRL7250 fibroblast cell line was lentivirally infected with either a V5-SS18 or V5-SS18-SSX expressing vector, selected for 48 hours with puromycin, then grown for 5 days, at which point cells were harvested for ChIP-seq preparation.

Data type: Epigenomics

Sample scope: Multiisolate

Relevance: Medical

Last updated: 2017-12-13