During in vivo OSKM induction, we observe increased chromatin accessibility at genes encoding apoptotic regulators, decreased H3K9me3 levels, and upregulation of histone demethylase Kdm3a. This OSKM-induced apoptosis phenotype can be mimicked when MLL-AF9 AML cells are treated with chaetocin, a small-molecule inhibitor of H3K9 methylation. The gene discussed is KMT2A; the disease is acute myeloid leukemia.