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| Status |
Public on May 31, 2018 |
| Title |
The SS18-SSX fusion oncoprotein hijacks BAF complex targeting and function to drive synovial sarcoma [ChIP-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
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.
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| 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.
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| Contributor(s) |
Pulice J, Kadoch C |
| Citation(s) |
29861296, 38539460 |
| |
| Submission date |
Dec 13, 2017 |
| Last update date |
Apr 04, 2024 |
| Contact name |
Cigall Kadoch |
| Organization name |
Dana-Farber Cancer Institute
|
| Department |
Pediatric Oncology
|
| Lab |
Kadoch Lab
|
| Street address |
450 Brookline Avenue
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (53)
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| This SubSeries is part of SuperSeries: |
| GSE108028 |
The SS18-SSX fusion oncoprotein hijacks BAF complex targeting and function to drive synovial sarcoma |
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| Relations |
| BioProject |
PRJNA422263 |
| SRA |
SRP126661 |
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