Extended Data Figure 4: Changes in genome-wide enrichment profiles of BRD proteins in response to bromodomain inhibitors.

a, Table showing high-throughput sequencing read information for ChIP libraries of BRD2, BRD3, BRD4, AR, RNA Pol II, ERG, H3K27ac and IgG performed for this study. b, ChIP-seq was performed using BRD2, BRD3 and BRD4 antibodies in VCaP cells treated with DMSO, JQ1 or I-BET762 for 12 h. Genome-wide distribution of BRD2, BRD3 and BRD4 enriched sites. Highly significant peaks (see Methods) show relatively high overlap. A large majority of sites are occupied by at least two BRD proteins. BRD2 and BRD3 have the most similar localization pattern. c, BRD proteins show varying degrees of overlap. Shown is the ratio of sites occupied by either protein alone (unique) or co-occupied with another BRD-family protein (overlap). BRD4 shows the largest number of unique peaks. d, BET inhibitors JQ1 and I-BET762 attenuate recruitment of BRD proteins from chromatin. Enrichment levels for each protein were normalized to the median enrichment in vehicle-treated cells. BRD2 and BRD3 proteins show similar responses to both inhibitors, whereas BRD4 is more potently evicted by JQ1. e, BET bromodomain inhibitors deplete target proteins from genomic regions with or without AR. Mean enrichment levels within each subpanel were normalized to the maximum mean enrichment in vehicle-treated cells.