Similar to acetylation and phosphorylation, histone methylation at the N-terminal tail has emerged as an important role in regulating chromatin dynamics and gene activity. Histone methylation occurs on arginine and lysine residues and is catalyzed by two families of proteins, the protein arginine methyltransferase family and the SET-domain-containing methyltransferase family. Five members have been identified in the arginine methyltransferase family. About 27 are grouped into the SET-domain family, and another 17 make up the PR domain family that is related to the SET domain family. The retinoblastoma protein-interacting zinc finger geneRIZ1 is a tumor suppressor gene and a FOUNDING member of the PR domain family. RIZ1 inactivation is commonly found in many types of human cancers and occurs through loss of mRNA expression, frame shift mutation, chromosomal deletion, and missense mutation. RIZ1 is also a tumor susceptibility gene in mice. The loss of RIZ1 mRNA in human cancers was shown to associate with DNA methylation of its promoter CpG island. Methylation of the RIZ1 promoter strongly correlated with lost or decreased RIZ1 mRNA expression in breast, liver, colon, and lung cancer cell lines as well as in liver cancer tissues.