Inhibition of cBAF activity impairs accessibility at RUNX1 binding sites, RUNX1 binding to the chromatin, and inhibits the RUNX1 transcriptional program. (A-B) ATAC-seq read-density heat maps from the indicated knockout Jurkat cells and ChIP-seq read-density heat maps of RUNX1 from Jurkat cells at genomic sites that are compacted (A, 9756 sites) or retained (B, 40 931 sites) in SMARCA4/2 knockout cells compared with control cells (gAAVS1). (C) Venn diagram showing the overlap between genomic sites compacted in the indicated knockouts. (D) Pie charts showing the fractions of promoter- and enhancer-associated compacted (top) and retained (bottom) sites identified in SMARCA4/2 knockout cells. (E-F) Top 3 motifs enriched within genomic sites compacted (E) or retained (F) in SMARCA4/2 knockout cells (HOMER, hypergeometric test, ranked by P value). (G) The proportions of the compacted and retained sites containing the RUNX1 motif. (H-I) Changes in chromatin accessibility at RUNX1 (H) and CTCF (I) binding sites in the indicated knockouts. (J) The proportion of RUNX1 and CTCF peaks compacted by SMARCA4/2 knockout. (K) ChIP-seq read-density heat maps of RUNX1 in the indicated knockout and control Jurkat cells at the compacted sites. (L) The proportion in the compacted sites relative to RUNX1 binding. (M-N) GSEA on transcriptomes of SMARCA4/2 and ARID1A/B knockout Jurkat cells (M) and BRM014-treated human T-ALL cell lines (N). Cells were treated with BRM014 at 1 μM for 6 hours (N). An in-house gene set consisting of RUNX1-regulated genes (supplemental Table 4) was used in panels M and N. GSEA, gene set enrichment analysis.