SET07 is a histone methyltransferase that methylates Lys-20 of histone H4. H4 Lys-20 methylation represents a specific tag for epigenetic transcriptional repression. The nuclear SET07 protein, which associates with silent chromatin on euchromatic arms but shows no association with constitutive heterochromatin, prefers nucleosomes as substrate compared to free histones. It appears that SET07 may play a role in maintaining silent chromatin by preventing neighboring acetylation of H4 tail. Although the SET domain contains the active site of enzymatic activity, both sequences upstream and downstream of the SET domain are required for methyltransferase activity.