A bifunctional nucleosome binding protein mediates specialized mSWI/SNF complex targeting and activity (ChIP-seq dataset)

Here we identify and characterize a minimal domain within the SS18-SSX fusion oncoprotein hallmark to synovial sarcoma, that exhibits a high-affinity interaction with the nucleosome acidic patch. We find that this region is necessary and sufficient for nucleosome binding, mSWI/SNF (BAF) chromatin remodeling complex targeting, catalytic activity, and activation of cancer-specific gene expression. Moreover, we identify PRC1-mediated H2AUb119 as a further rheostat governing further stability and binding. Together, our results define an unexpected direct bifunctional histone detector on SSX that is responsible for disease-specific chromatin recruitment of a major family of chromatin regulatory complexes. Overall design: Expression constructs of V5-tagged SS18-SSX fusion or specific fusion mutations were overexpressed in CRL7250 human fibroblast cells to determine the role of specific amino acids in directing the chromatin targeting of this fusion. Alternatively, shRNA hairpins targeting the SS18-SSX fusion in synovial sarcoma cell lines were expressed to see how the chromatin targeting of mSWI/SNF complexes or polycomb complexes and the histone landscape is altered upon loss of the fusion.