Figure 2.

Fusion oncoprotein-bound mSWI/SNF complexes activate oncogenic transcription via cancer-specific genomic targeting. (A) In synovial sarcoma, the SS18–SSX fusion is incorporated into BAF complexes, resulting in the eviction of wild-type SS18 and BAF47 subunits. These SS18–SSX-containing complexes are targeted to sites of PRC2-mediated repression, such as SOX2, leading to a reduction in H3K27me3 levels and activation of transcription. (B) In Ewing sarcoma, the EWS–FLI1 fusion transiently interacts with BAF complexes and results in cancer-specific targeting to GGAA microsatellites. This de novo targeting of BAF complexes leads to increased H3K27ac levels, enhancer activation, and oncogenic transcription.