Methylation of lysine can promote transcriptional activation or repression and is critical in regulating histone function. Lysine residues can be mono-, di-, or tri-methylated. SET8 selectively mono-methylates histone H4 at lysine 20, an event proven to have an important role in chromatin structure and transcriptional activation. SET8 is also a novel regulator of p53, mono-methylating lysine 382 of the tumor suppressor. SET8's ability to suppress p53 transcriptional activity implies that it may play a significant role in tumorigenesis.