Fig. 3. SWI/SNF ATPase degradation disrupts enhancer–promoter loops to temper supra-physiologic expression of driver oncogenes.
a, Immunoblots of indicated proteins in VCaP cells treated with DMSO for 24 h or AU-15330 (1 μM) for increasing time durations. GAPDH is used as a loading control, and is probed on a representative immunoblot. This experiment was repeated independently twice. b, H3K27Ac ChIP–seq signal rank-ordered list of super-enhancers in VCaP cells with select cis-coded driver oncogenes denoted (HOMER). c, Normalized read density of ATAC-seq at super-enhancers (n = 32,545 sites) in VCaP cells treated with DMSO or AU-15330 (1 μM) for 1 or 4 h (two-sided t-test). In box plots, the centre line shows median, box edges mark quartiles 1–3, and whiskers span quartiles 1–3 ± 1.5 × interquartile range. d, H3K4me3 HiChIP–seq heat maps within the AR gene locus in VCaP cells with or without AU-15330 (1 μM) treatment for 4 h (bin size = 25 kb). ATAC-seq read-density tracks from the same treatment conditions are overlaid. Grey highlights mark enhancers; blue highlights the AR promoter. Loops indicate read-supported cis interactions within the locus. IR, interaction reads. e, APA plots for H3K4me3 and H3K27Ac HiChIP–seq data for all possible interactions between putative enhancers and gene promoters in VCaP cells with or without with AU-15330 treatment (1 μM, 4 h).