RNA-seq profiling of mouse embyonic fibroblasts treated with the Myst inhibitor WM-8014

Acetylation of histones by lysine acetyltransferases (KATs) is essential for transcriptional regulation of gene expression. The MYST family of KATs (KAT5-8) includes the oncogenes KAT6A (MOZ) and KAT6B (MORF/QKF). KAT6A has key roles in promoting cell proliferation through transcriptional activation of negative regulators of the Cdkn2a locus, which encode the tumor suppressors INK4A and ARF. We produced a series of highly potent, selective inhibitors of KAT6A/B including WM-8014 and WM-1119. Biochemical and structural studies demonstrate that these compounds are reversible acetyl-CoA competitors. WM-8014 and WM-1119 inhibit MYST-catalyzed histone acetylation, thereby inducing cell cycle exit and cellular senescence, without causing DNA damage. The data here examine the transcriptional effects of WM-8014. Mouse embryonic fibroblasts (MEFs) were treated with either WM-8014 or with WM-2474, an inactive control, for either 96 hours or 240 hours and RNA-seq profiling was undertaken. Three biological replicates were prepared and sequenced. RNA-seq was undertaken for n=3 MEF samples treated with WM-2474 for 96 hours, n=3 MEF samples treated with WM-2474 for 240 hours, n=3 MEF samples treated with WM-8014 for 96 hours and n=3 MEF samples treated with WM-8014 for 240 hours.