Fig. 7: Addition of TAK-981 results in loss of chromatin accessibility to promoters of the SS18::SSX transcriptome.

A, B Boxplots demonstrating distribution of SYO-1 and HS-SY-II ATAC-seq peaks genome-wide after 100 nM of TAK-981 treatment (72 h) (n = 3 biological replicates for No Rx and n = 3 biological replicates for TAK-981-treated SYO-1 cells and n = 4 biological replicates for No Rx and n = 4 biological replicates for TAK-981 treated HS-SY-II cells), focusing on downregulated RNA-seq normalized genes for HS-SY-II cells transduced with SS18::SSX shRNA from Banito et al.²². Differential accessibility peaks were annotated using the ChIPseeker v.1.40.0 R package and percentages of peaks associated with various gene-centric annotations were compared using unpaired two-sided t test. The boxplots show the median (central line), and the interquartile range of the data. The whiskers extend to the minimum and to the maximum values excluding outliers. C SYO-1 and HS-SY-II ATAC-seq profiles after TAK-981 treatment focusing on downregulated RNA-seq normalized genes of HS-SY-II cells transduced with SS18::SSX shRNA²² (the same list of downregulated genes used in (A, B), centered on TSS (transcription starting sites). For calculating the p values two-sided Wilcoxon tests were performed. D Schema of changes at the chromatin following TAK-981 treatment in SS. E, F Heatmaps of jointly clustered row-normalized gene expression (RNA-seq), and signal (ATAC-seq, ChIP-seq) of the top 1000 most upregulated genes and the associated peaks before and after TAK-981 treatment (number of replicates for each condition, n = 3). G Model of TAK-981 efficacy. TAK-981 deSUMOylates SMARCE1, leading to its accumulation. SMARCE1 upregulation leads to cBAF complex stabilization and redistribution of the BAF complexes (towards a normal cell phenotype) (D, G) were created in BioRender. Floros, K. (2025).