The genomic methylation patterns in the mammalian somatic cells are presumably maintained by a single enzyme, dnmt1. In mouse, this DNA (cytosine-5)-methyltransferase, or CpG MTase, is encoded by the Dnmt1 gene. We now present evidence that in different tissues and cell types, the primary transcript of mouse dnmt1 is alternatively spliced to generate two poly-(A) RNAs of approximately similar abundance. This alternative splicing most likely originates from the existence of two tandemly arranged acceptor sites separated by only 3 nt. The two Dnmt1 mRNAs thus encode two CpG MTases differing by two amino acids. We discuss the implications of the discovery of two dnmt1 isozymes, instead of one enzyme as previously thought, in the somatic cells of both mouse and human.
