SET and invasive breast carcinoma: It is observed in our structure that the breast-invasive carcinoma and lung adenocarcinoma cancer-associated mutations S255F27 and S283L28 with larger sidechains block the insertion of the H4 tail into SUV420H1 SET domain at the entrance site (Supplementary Fig. S4b), thus inhibiting the methylation activity of SUV420H1 confirmed by in vitro and in vivo assays20.