Figure 1. Compensation for the exclusion of BRD4 from chromatin via BET inhibition occurs through acute redistribution of p300 to critical AML maintenance genes.

A.Correlation of nucRNASeq with BRD4 binding dynamics in DMSO versus BETi-treated KASUMI-1 cells. Shown are signals that matched to both BRD4 and nucRNASeq peaks. Signals were annotated to the nearest promoters.

B. Correlation of SLAMSeq with BRD4 binding dynamics in DMSO versus BETi-treated SKNO1 cells. BRD4 peaks were annotated to the nearest promoters and matched to the corresponding 3’UTR regions from SLAMSeq.

C. Examples of BRD4 binding and nucRNASeq profiles in DMSO and BETi-treated KASUMI-1 cells, to demonstrate the rescue of mRNA production at/near promoters of the main RUNX1 isoforms and CDK6 upon BETi, but not at/near the BLACE or GPR85 promoters.

D. Analysis of qPCR expression of the indicated transcripts/genes in KASUMI-1 and SKNO1 cells after treatment with either DMSO or BETi (24h). Shown are log2 Fold Changes normalized to DMSO-treated controls and SD from 3 biological replicates.

E. SLAMSeq intensity at the 933 rescued genes at 0 hr (DMSO), 4 hr and 24 hr following BET inhibition. Shown are log2 fold change ratios compared to 0 hr (DMSO-treated controls). Three biological replicates were acquired per condition/time point.

F. SLAMSeq intensity at the indicated exemplar rescued genes at 0 hr (DMSO), 4 hr and 24 hr following BET inhibition. Shown are log2 fold change ratios compared to 0 hr (DMSO-treated controls). Three biological replicates were acquired per condition/time point.

G. Average binding curve profiles for BRD4, p300, RUNX1, FLI1, RUNX1-RUNX1T1 and H3K27ac in DMSO and BETi-treated KASUMI-1 cells, to demonstrate the BETi-triggered increase of p300 and RUNX1 binding at/near the rescued genes.

H. Average binding curve profiles for BRD4 and p300 in DMSO and BETi-treated SKNO1 cells, to demonstrate the BETi-triggered increase of p300 binding at/near the rescued genes.