Figure 6.
Inhibition of RNA Pol2 engagement, transcript, and protein expression of driver genes in cluster I after HDAC inhibition. (A) Effect of HDAC inhibition on RNA Pol II occupancy at promoters. RNA Pol II ChIP-seq gene profiles showing changes in log2 read counts per million (log2 CPM) for RNA Pol II occupancy from −5 to -1kb of the PP centered around the TSS to +3 to +6 KB of the GB at BCL2, BLK, PAX5, IKZF3, miR-155, BTK, ROR1, and SYK in 1 of 3 representative CLL samples (CLL251228) before (blue) and after exposure to 0.4 μM abexinostat for 24 hours (red). (B) Validation of RNA seq results using RT-PCR expression assays quantitating changes in expression levels of selected genes from cluster I ([i-ix]-BCL2, BLK, PAX5, IKZF3, BTK, miR-155, ROR1, SYK, and CD27) from 10 CLL samples before and after exposure to abexinostat for 24 hours. ∗, ∗∗, ∗∗∗, ∗∗∗∗ P < .5, .01, .001, .0001, Student t test, Graph pad software. (C) Change in protein expression of select driver genes in 5 CLL samples before and after exposure to 0.4 μM, abexinostat for 24 hours. GB, gene body; PP, proximal promoter.