Histone methyltransferase (HMT)(1) class enzymes that methylate lysine residues 
of histones or proteins contain a conserved catalytic core termed the SET 
domain, which shares sequence homology with an independently described sequence 
motif, the PR domain. Intact PR or SET sequence is required for tumor 
suppression functions, but it remains unclear whether it is histone 
methyltransferase activity that underlies tumor suppression. We now show that 
tumor suppressor RIZ1 (PRDM2) methylates histone H3 on lysine 9, and this 
activity is reduced by mutations in the PR domain found in human cancers. Also, 
S-adenosylhomocysteine or methyl donor deficiency inhibits RIZ1 and other H3 
lysine 9 methylation activities. These results support the hypothesis that H3 
lysine 9 methylation activities of a PR/SET domain have tumor suppression 
functions and may underlie carcinogenesis associated with dietary methyl donor 
deficiency.