Extended Data Fig. 6. The canonical SWI/SNF complex is the primary cofactor of enhancer-binding transcription factors and is essential for enabling their oncogenic gene programs.
(a, c) Genome-wide ChIP-seq read-density heatmaps and Venn diagrams for CTCF in VCaP (a) or LNCaP (c) cells treated with either DMSO or AU-15330 (1 μM) for 6h. Vinculin is the loading control probed on a representative immunoblot. (b, d) Immunoblots of indicated proteins in VCaP (b) or LNCaP (d) cells treated with AU-15330 (1 μM) for increasing time durations. Total histone H3 is the loading control probed on all immunoblots. This experiment was repeated independently twice. (e) GSEA plots for ERG, FOXA1, and MYC-regulated genes using the fold change rank-ordered gene signature from AU-15330-treated (1 nM, 24h) VCaP cells. NES, net enrichment score; adj P, adjusted p-value; DEGs, differentially expressed genes. (f, g) GSEA of FOXA1, MYC, or ARID1A-regulated genes (see Methods for gene sets) in the fold change rank-ordered AU-15330 gene signature in indicated PCa cells. DEGs, differentially expressed genes. (n = 2 biological replicates, GSEA enrichment test) (h, i) Expression of indicated genes (qPCR) in VCaP (h) or LNCaP (i) cells upon treatment with DMSO, AU-15330, dBRD7 (BRD7 degrader), or dBRD7/9 (dual BRD7 and BRD9 degrader) at 1 μM for 24h. Data are presented as mean +/− SD (n = 3, technical replicates) from one-of-two independent experiments. (j) Immunoblots for indicated proteins in LNCaP and VCaP cells treated with AU-15330, dBRD9 (BRD9 degrader), or VZ185 (BRD7/9 degrader) at indicated concentrations. Vinculin is the loading control probed on all immunoblots. This experiment was repeated independently twice.