Extended Data Figure 6: Effect of JQ1 on the TMPRSS2-ERG loci and ERG-mediated transcription in VCaP cells.

a, Genome browser representation of RNA Pol II binding events within the ERG gene body. The y-axis denotes reads per million mapped reads per base pair (r.p.m. bp⁻¹), the x-axis denotes the genomic position and the black arrow indicates the region involved in the TMPRSS2-ERG fusion. b, As in a, AR and BRD4 binding on the promoter of the ERG 5′-fusion partner TMPRSS2 in VCaP cells. Note the reduced RNA Pol II and AR–BRD4 recruitment levels in DHT plus JQ1 tracks for the ERG gene body and TMPRSS2 promoter respectively. c, High reproducibility of ERG ChIP-seq experiments. Biological replicates of ERG ChIP-seq experiments show very high correlation of normalized enrichment levels (see Methods) in the JQ1- and DMSO-treated conditions. d, Significant changes in ERG levels upon JQ1 treatment at ERG-binding sites in the proximity of gene loci. Changes in ERG enrichment levels were assessed using DESeq2. Statistically significant differences were observed for ERG gain and ERG loss. Significant ERG gains are associated with quantitatively modest changes in enrichment level. On the other hand, significant ERG losses are associated with greater changes in enrichment levels. Individual number of peaks for each panel is shown. e, Genome browser representation of ERG-binding events on bona fide ERG-activating target genes. The y-axis denotes reads per million per base pair (r.p.m. bp⁻¹), the x-axis denotes the genomic position. f, Genome browser representation of ERG-binding events on ERG-repressed target genes. g, TaqMan qRT–PCR analysis of ERG-activated genes in VCaP cells after JQ1 treatment. h, TaqMan QRT–PCR analysis of ERG-repressed genes in VCaP cells after JQ1 treatment. Data represent mean ± standard deviation (s.d.) (n = 3) from one of two independent experiments. *P ≤ 0.05; **P ≤ 0.005, ***P ≤ 0.0005 by two-tailed Student’s t-test.