Structure of mammalian DNA methyltransferase as deduced from the inferred amino acid sequence and direct studies of the protein.

DNA (cytosine-5)-methyltransferase (DNA MeTase) establishes and maintains methylation patterns in the genome of higher eukaryotes. This enzyme has been purified, and the cDNA which encodes it has been cloned and sequenced. DNA MeTase appears to contain a large (1000 amino acid) N-terminal domain that contains potential metal-binding sites. This domain appears to contain a series of five to seven structural units of Mr about 20,000, since post-translational processing in vivo or partial proteolysis of the purified protein in vitro leads to the production of a series of catalytically active species differing in Mr by units of 20,000. The N-terminal domain is fused to a smaller (570 amino acid) C-terminal domain that is related to bacterial type II cytosine methyltransferases. The relevance of these findings for the biological function of DNA MeTase is discussed.