Interestingly, a recent study has reported that doxycycline-regulated overexpression of an H3K36M onco-histone transgene in mice resulted in a highly similar, fully penetrant erythroleukemia-like phenotype.5 Notably, the H3K36M-mutant nucleosomes dominantly inhibit the enzymatic activities of H3K36 KMTs, including NSD1, resulting in reduced H3K36 mono- and di-methylation. Here, NSD1 is linked to erythroleukemia.