HDAC inhibition causes dynamic changes in the occupancy of HDAC1, H3K9Ac, BRD4, and RNA Pol2 engagement to downregulate driver genes in cluster I. (A) Gene expression heat map obtained after total RNA seq of 10 CLL samples treated with the HDAC inhibitor abexinostat (0.4 μM, 24 hours) compared with untreated controls. 621 differentially expressed PCG that showed an absolute fold change of 2 or more at 10% FDR, of which 329 (54%) decreased and 292 (47%) genes increased expression. Key CLL driver genes, such as IKZF3, CD27, SYK, BTK, mir-155, IKZF1, BLK, PAX5, and ROR1, were among the downregulated transcripts. (B) Genome browser tracks showing the change in HDAC1 (red), BRD4 (turquoise), H3K9Ac (green), H3K27Ac (olive), RNA Pol II (violet), ATAC seq peaks (brown) in a representative CLL sample out of 3 at baseline and after exposure to 0.4 μM abexinostat for 6 hours, HDAC1 (yellow), BRD4 (blue), H3K9Ac (mint), H3K27Ac (green), RNA Pol II (mauve), and ATAC seq peaks (orange) are shown for select genes such as CXCR4, IL4R, BCL2, IKZF3, PAX5, and BLK. The x-axis of each track shows genomic position, and the y-axis shows the intensity of the ChIP signal (rpm/bp).