Fig. 3

CDK9 inhibition reprograms the promoter and enhancer landscape. OCI-LY3 and VAL cells were treated with AZD4573 (30 nM) for 0, 3 and 8 h prior to harvest. After 8 h exposure, the compound was washed out and cells were harvested after 24 h. Samples were analyzed using ATAC-seq and ChIP-seq. A Differential ATAC-seq peaks were calculated using DESeq2 software (|FC| ≥|1.5|; padj ≤ 0.05). Significantly gained and lost peaks are considered regions of increased and decreased chromatin accessibility, respectively. B Table of top enriched motifs in regions of decreased chromatin accessibility in ATAC-seq. Table includes position weight matrices of nucleotide sequences comprising motifs identified using gene-based HOMER motif analysis. C Metagene analysis of normalized H3K4me3 and H3K27ac ChIP-seq signal intensity plots for all human UCSC genes ± 3 kb of the transcription start site. Gene tracks are shown highlighting the PIM3 locus. D Representative hockey stick plot of super enhancers in Val and OCI-LY3 cell lines. Enhancers were identified and ranked based on H3K27ac ChIP-seq read density as a percentage of total signal, and labeled with the nearest gene. Enhancer ranking was carried out using the ROSE2 algorithm with default parameters. The number of super enhancers per sample is shown in black. SE-associated genes are depicted as red dots. Ranks of 5 top SE-associated oncogenes are included in parenthesis. E Heatmap depicting Z-score of genes with differential SEs in VAL cells at 24 versus 0 h of treatment with AZD4573, performed in duplicate