Jeong et al. revealed that the catalytic activity of histone methyltransferase nuclear SET domain-containing protein 3 (NSD3) toward H3K36 methylation induces dimethylated or trimethylated histone H3 at lysine 36 (H3K36me2/3) dependent transactivation of genes connected with NOTCH signaling, driving breast tumor initiation and metastasis by the NSD3/NOTCH signaling regulatory axis [5]. The gene discussed is NSD3; the disease is breast neoplasm.