Extended Data Fig. 7: SWI/SNF inhibition down-regulates the expression of oncogenic drivers through disruption of promoter and super-enhancer interactions.
From: Targeting SWI/SNF ATPases in enhancer-addicted prostate cancer
(a, b) RNA expression (RNA-seq) heatmaps from VCaP or LNCaP cells treated with DMSO, AU-15330 (1 μM), or ZBC-260 (BRD4 degrader) for the noted durations. n = 2, biological replicates. (c) RNA expression (qPCR) of indicated genes in stable CRISPR-engineered LNCaP-sgNC (control) or LNCaP-sgSMARCA2 (SMARCA2 inactivation) cells that were treated with a non-target control shRNA or two distinct shRNAs targeting the SMARCA4 gene. Data are presented as mean +/− SD (n = 3, technical replicates) from one-of-two independent experiments. Right, immunoblots showing expression of the indicated protein in CRISPR/shRNA-engineered LNCaP cells. Vinculin is the loading control probed on a representative immunoblot. This experiment was repeated independently twice. (d) Normalized read density of AR, FOXA1 and H3K27Ac ChIP-seq signal at the super-enhancer sites (n = 1,551 sites) in VCaP cells treated with DMSO or AU-15330 (1 μM) for 4h or H3K27Ac with 24h AU-15330 (two-sided t-test). For all box plots, the center shows median, box marks quartiles 1–3, and whiskers span quartiles 1–3 ± 1.5 × IQR.
