ChIP-seq of GLTSCR1 and SS18::SSX fusion in HS-SY-II synovial sarcoma cells treated with the BRD9 PROTAC degrader WA-68 across a time course

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.