ATAC-seq of synovial sarcoma cell lines treated with the BRD9 PROTAC degrader WA-68

Synovial sarcoma (SyS) is driven by the SS18::SSX fusion oncoprotein, which incorporates into GBAF chromatin remodeling complexes and creates a dependency on BRD9. To investigate the effects of BRD9 loss, we performed ChIP-seq, ATAC-seq, and RNA-seq in SyS models following BRD9 degradation. ChIP-seq shows reduced GBAF occupancy at target loci, while ATAC-seq reveals maintained or increased chromatin accessibility. RNA-seq demonstrates sustained or elevated expression of target genes. These results indicate that BRD9 is not required for GBAF assembly but instead restrains its remodeling activity, providing a mechanistic explanation for the limited efficacy of BRD9-targeted therapies in SyS.