Fig. 4

BRD4 enhances transcriptional recovery. A OCI-LY3 cells were treated with AZD4573 for 0, 3 and 8 h prior to harvest. After 8 h exposure, the compound was washed off and cells were harvested after 24 h. Samples were analyzed by ChIP-seq for BRD4 and RBP1. Data is shown as normalized ChIP-seq signal intensity plots for all human UCSC genes ± 2 kb, as well as snapshots of select gene tracks. B DLBCL cell lines were treated with AZD4573 (3 nM) and the BET-bromodomain inhibitor JQ1 (50 nM) as single agents or in combination for 48 h. Proliferation was analyzed using a colorimetric tetrazolium-based assay. Data is shown as mean ± SEM of three independent experiments. *p < 0.05 and **p < 0.01 vs. untreated control unless otherwise notated. C Gene expression fold change of select genes following treatment with AZD4573 at 30 nM, JQ1 at 1 µM, or a combination of the two in VAL and OCI-LY3 cell lines, determined by RT-PCR. Cells were treated for 0, 3 and 8 h prior to harvest. After 8 h exposure, the compound was either washed out (w) or not (c = continuous exposure) and cells were harvested after 24 h. Data is shown as mean ± SEM of three independent experiments. *p < 0.05 and **p < 0.01 vs. time-matched DMSO control