In the same issue of Nature, a simultaneous study by Li et al. solved the cryo-electron microscopy structures of NSD2 and NSD3 as well as their cancer-related hyperactive variants bound to mononucleosomes.2 They found that binding of NSD2 or NSD3 to the nucleosomes unwrap the DNA near the linker region, which makes the catalytic core insert between the unwrapped DNA and histone octamer. Here, NSD3 is linked to cancer.