Fig. 6: Transcriptomic changes caused by BRPF1 inhibition indicate ribosome biogenesis defects.

a Volcano plots showing differentially expressed genes (P < 0.05) after 72 h of PFI-4 (5 µM) (left) and OF-1 (5 µM) (right) treatment on T1-160 cells. b Volcano plots showing differentially expressed genes (P < 0.05) upon BRPF1 KO with sgRNA #2 and #3 compared with nontargeting control (NT1) on T1-160 cells. c A heatmap showing the mRNA expression levels of all genes that were commonly downregulated or upregulated in BRPF1 inhibitor-treated or sgRNA-infected cells. On the right, significant pathways of the common upregulated and downregulated genes are demonstrated by the overlap analysis via MsigDB. d A balloon plot depicting the LFCs and adjusted P values of ribosome-related genes in BRPF1-KO cells. e SUnSET assay showing global translation levels in control and BRPF1-KO cells. Band intensities were normalized to the loading control GAPDH, and the ratio of NT1 sample was normalized to 1. f A comparison of the genes upregulated in T1-160 cells and downregulated in BRPF1-KO T1-160 cells. g Western blot showing ABCB1 protein levels in BRPF1-KO T1-160 cells. h The ABCB1 gene structure with the locations of the primers used in the CUT&RUN-qPCR experiment. i, CUT&RUN-qPCR results showing the enrichment of BRPF1 binding sites on ABCB1 and RPL24 promoters in T1-160 cells expressing HA-tagged BRPF1. P values determined by two-tailed Student’s t-test by comparing each HA group with its IgG control; *P < 0.05, **P < 0.01, ***P < 0.001. j, CUT&RUN-qPCR results showing the decrease in the enrichments of H3K27Ac, H3K14Ac and H3K9Ac histone marks on ABCB1 and RPL24 promoters upon BRPF1 loss. Data are representative of three independent biological replicates. P values determined by two-way ANOVA with Tukey’s post-hoc test; *P < 0.05, **P < 0.01, ***P < 0.001.