Genome-wide loss of mSWI/SNF and PRC2 complex activity and targeting results in oncogenic transcription. (A) In BAF47-deficient sarcomas, such as malignant rhabdoid tumor and epithelioid sarcoma, the loss of BAF47 incorporation into BAF and PBAF complexes results in residual complexes with decreased chromatin affinity. BAF complex occupancy and H3K27ac levels are reduced genome-wide at enhancers and PBAF complexes are attenuated at gene promoters, while PRC2 occupancy increases at active gene promoters, leading to deposition of H3K27me3 and the creation of transcriptionally-silent bivalent gene promoters. (B) In cases of malignant peripheral nerve sheath tumors with SUZ12 or EED subunit loss, PRC2 occupancy and H3K27me3 levels are reduced, contributing to increased activation of oncogenic transcription.