Extended Data Fig. 8: Dual SMARCA2 and SMARCA4 degradation by PROTAC leads to accessibility changes correlating with changes observed after inhibition of both ATPases.

a, Western blot analysis of HAP1 cell cytoplasm, nucleoplasm and chromatin fraction after ACBI1 treatment (cropped images). b, Volcano plots displaying the chromatin accessibility changes in HAP1 cells after ACBI1 treatment compared to DMSO control for 6 h and 72 h treatment. Significant changes (Padj <0.01 and abs(log₂(fold-change)) >1) are colored in red. (c, left) Scatter plot of log₂(fold-change) of chromatin accessibility after 24 h dTAG47 treatment of SMARCA4^dTAG versus DMSO control (y-axis) against log₂(fold-change) of chromatin accessibility after 24 h ACBI1 treatment of WT cells versus DMSO control (x-axis). Pearson correlation coefficient is depicted. (c, right) Scatter plot of log₂(fold-change) of chromatin accessibility after 24 h BRM014 treatment versus DMSO control (y-axis) and log₂(fold-change) of chromatin accessibility after 24 h ACBI1 treatment of WT cells versus DMSO control (x-axis). Pearson correlation coefficient is depicted. d, Heatmap of accessibility changes measured as log₂(fold-change) after BRM014 or ACBI1 treatment versus DMSO control for the 5 clusters from Fig. 3a.