BET inhibitors suppress lytic DNA replication.
A, flow cytometry analysis of BZLF1 staining in Akata-Zta cells treated with doxycycline (Dox). Error bars show the standard deviation of n = 4 replicates. B, RNA-seq profiles of treated Akata-Zta cells showing the entire EBV genome (top) or the region containing the BZLF1 gene (inset). Axes denote genomic position in base pairs and counts per million mapped reads. Some major peaks corresponding to lytic gene expression are labeled. Below the inset, the BZLF1 gene is shown in schematic form where blocks represent exons and lines with arrows represent introns. Results are representative of three independent biological replicates. C, -fold change in EBV DNA from treated Akata-Zta cells based on deep sequencing of chromatin. EBV content was calculated as a percentage of total sequenced DNA, and for each set, EBV DNA was normalized to that in the vehicle-treated sample. Error bars represent the standard deviation of n = 3 replicates.