Extended Data Fig. 7: BRD4 chromatin occupancy displays differential BETi sensitivity at super-enhancer versus promoter regions.

(a) Ranking of enhancers (pink) by BRD4 signal versus signal at a given enhancer based on BRD4 ChIP-seq in keratinocytes per condition as indicated identifies super-enhancers (blue). (b) Genome browser track view of BRD4 occupancy (ChIP-seq signal) at HIST2H2BE genomic locus upon treatment conditions as indicated. Chromosome coordinates as well as super-enhancer and promoter locations labeled, with H3K27ac ChIP-seq data taken from low-passage untreated HPEK and ChromHMM taken from ENCODE NHEK. (c) MSigDB gene set enrichment analysis of genes associated based on proximity with BRD4 ChIP-seq peaks found to be significantly upregulated at 6 h with 125 nM NVS-BET-1 compared to DMSO as shown in Fig. 4b. (d) CpG content analysis of top 100 down- or upregulated BRD4 ChIP-seq peaks overlapping promoters (at 6 h with 125 nM NVS-BET-1 treatment compared to DMSO). Promoters defined as per NHEK ChromHMM, with top 100 down corresponding to 100 active promoters versus top 100 up classified as 25 active and 75 inactive promoters. Thick dotted lines represent median and thin dotted lines quartiles.