Extended Data Fig. 3: The effect of WM-8014 on cell proliferation is mediated through the cell cycle regulators p16INK4A and p19ARF.
From: Inhibitors of histone acetyltransferases KAT6A/B induce senescence and arrest tumour growth
a, RT–qPCR analysis of expression levels of cell cycle regulators Ink4a and Arf (alternative splice products of the Cdkn2a locus), Ink4b (also known as Cdkn2b) and Cdkn1a (encoding p21WAF1/CIP1) mRNA in MEFs treated for 4 days and 10 days with 10 µM WM-8014 or 10 µM control WM-2474. b, Dose–response plots of WM-8014 induction of Ink4a mRNA expression in MEFs. c, RT–qPCR analysis of expression changes in the KAT6A target gene detected by RNA-seq. MEFs were treated for 4 days and 10 days with 10 µM WM-8014, 10 µM control WM-2474 or DMSO. d, Dose–response plots of WM-8014-dependent reduction in E2f2 and Cdc6 mRNA levels in MEFs. e, Levels of mRNA coding for MYST-family proteins after treatment of MEFs for 4 days or 10 days with WM-8014, vehicle or the inactive compound WM-2474. n = 3 MEF isolates treated with WM-8014, WM-2474 or vehicle (a–e). Data are mean ± s.e.m. and are analysed by one-way ANOVA followed by Bonferroni post hoc test (a–c, e) and by regression analysis (d). mRNA levels normalized to housekeeping genes (HK) were regressed on the log(concentration) of WM-8014 (d).
