Figure S7 from BRD9 Degraders Unleash GBAF Chromatin Remodeling Activity in Synovial Sarcoma

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Supplemental Figure S7 (associated with Figure 7). GBAF remodeler sliding activity increases in the absence of BRD9. A. RNA-seq defined differential expression comparing WA-68 exposure to control DMSO in a control set of maintained active transcription (MAT, expressed genes without fusion and H2AK119ub targeting) following BRD9 degradation in SYO-1 cells. B. Differential expression of sarcomagenesis silenced transcription (SST, not significantly expressed in vehicle treated cells) genes following BRD9 degradation or control in SYO-1 cells. C. Titration sliding assays showing slid and ejected fractions after 60 minutes at variable molar ratios of recombinant nucleosomes to recombinant GBAF with or without BRD9 omitted. Recombinant nucleosomes include H3.3A refers to histone H3.3 variant with C110A mutation introduced to avoid ubiquitin transfer to this residue. Titration assays on recombinant nucleosomes that bear H2A ubiquitination in the octamer show no effect on nucleosome sliding for GBAF wild-type or GBAF lacking BRD9. The absence of BRD9 increases the overall sliding by GBAF. D. Heatmaps and enrichment plots from ATAC-seq and ChIP-seq for GLTSCR1 and SS18::SSX (by HA-tag) at genome-wide distal ATAC-seq sites in the HS-SY-II cell line after exposure to control DMSO or 12, 24, 48, or 96 hours of WA-68 E. The same at loci defined a priori by distal co-localization of called peaks for H2AK119ub, GLTSCR1, and SS18::SSX, termed sarcomagenesis activated transcription (SAT) sites.

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