The genomic methylation patterns in the mammalian somatic cells are presuma
bly maintained by a single enzyme, dnmt1, In mouse, this DNA (cytosine-5)-m
ethyltransferase, or CpG MTase, is encoded by the Dnmt1 gene. We now presen
t evidence that in different tissues and cell types, the primary transcript
of mouse dnmt1 is alternatively spliced to generate two poly-(A) RNAs of a
pproximately similar abundance, This alternative splicing most likely origi
nates 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 t
wo amino acids, We discuss the implications of the discovery of two dnmt1 i
sozymes, instead of one enzyme as previously thought, in the somatic cells
of both mouse and human. (C) 2000 Federation of European Biochemical Societ
ies.