Sequential pharmacological BET inhibition followed by p300 inhibition counteracts the expression of rescued programs. (A-D) Volcano plots (left) showing RNA-Seq expression changes in the indicated cell lines after 24 hours of treatment with DMSO or p300i. Dot plots (middle) of GSEA normalized enrichment scores (NESs) and false discovery rate q value significance of the top-scoring data sets after treatment with either DMSO or p300i for 24 hours in the indicated cell lines. Analysis of qPCR expression of MYC and BCL2 in the indicated AML cell lines (right) after treatment with either DMSO (48 hours of treatment), BETi (48 hours), p300i (24 hours), or sequential BETi and p300i (48 hours/24 hours). Shown are log2 FCs normalized to DMSO-treated controls and SD from 3 biological replicates. (E) Analysis of qPCR expression of the indicated transcripts/genes in SKNO1 cells after treatment with either DMSO (48 hours of treatment), BETi (48 hours), p300i (24 hours), or sequential BETi and p300i (48 hours/24 hours). Shown are log2 FCs normalized to DMSO-treated controls and SD from 3 biological replicates. GSEA, gene set enrichment analysis.
FigureĀ 3.

Sequential pharmacological BET inhibition followed by p300 inhibition counteracts the expression of rescued programs. (A-D) Volcano plots (left) showing RNA-Seq expression changes in the indicated cell lines after 24 hours of treatment with DMSO or p300i. Dot plots (middle) of GSEA normalized enrichment scores (NESs) and false discovery rate q value significance of the top-scoring data sets after treatment with either DMSO or p300i for 24 hours in the indicated cell lines. Analysis of qPCR expression of MYC and BCL2 in the indicated AML cell lines (right) after treatment with either DMSO (48 hours of treatment), BETi (48 hours), p300i (24 hours), or sequential BETi and p300i (48 hours/24 hours). Shown are log2 FCs normalized to DMSO-treated controls and SD from 3 biological replicates. (E) Analysis of qPCR expression of the indicated transcripts/genes in SKNO1 cells after treatment with either DMSO (48 hours of treatment), BETi (48 hours), p300i (24 hours), or sequential BETi and p300i (48 hours/24 hours). Shown are log2 FCs normalized to DMSO-treated controls and SD from 3 biological replicates. GSEA, gene set enrichment analysis.

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