NSD3 (also known as WHSC1L1), a Su(var)3-9, enhancer-of-zeste and trithorax (SET) domain containing histone lysine methyltransferase, can dimethylate and trimethylate histone H3 at lysine 36. In addition to the catalytic SET domain with pre- and post-SET domains, NSD3 possesses two PWWP (the conserved sequence motif of Pro-Trp-TrpPro) domains and five PHD (plant homeodomain) fingers, both of which are often involved in chromatin-associated biological processes through crosstalks with histone and DNA reader or modifier proteins. Hence, NSD3 is involved in a variety of biological processes such as chromatin modification, transcriptional regulation, and DNA repair either through direct regulation of histone methylation or through the protein-protein interactions by these specific domains. There are two major isoforms of NSD3, the long full-length isoform and the short isoform lacking the SET domain and only possessing the first N-terminal PWWP domain.
