Thus far, only one major form of vertebrate DNA (cytosine-5) methyltransfer
ase (CpG MTase, EC 2.1.1.37) has been identified, cloned, and extensively s
tudied. This enzyme, dnmt1, has been hypothesized to be responsible for mos
t of the maintenance as well as the de novo methylation activities occur ri
ng in the somatic cells of vertebrates. We now report the discovery of anot
her abundant species of CpG MTase in various types of human cell lines and
somatic tissues. Interestingly, the mRNA encoding this CpG MTase results fr
om alternative splicing of the primary transcript from the Dnmt1 gene, whic
h incorporates in frame an additional 48 nt between exons 4 and 5, Furtherm
ore, this 48-nt exon sequence is derived from the first, or the most upstre
am, copy of a set of seven different Alu repeats located in intron 4. The r
atios of expression of this mRNA to the expression of the previously known,
shorter Dnmt1 mRNA species, as estimated by semiquantitative reverse trans
cription-PCR analysis, range from two-thirds to three-sevenths. This altern
ative splicing scheme of the Dnmt1 transcript seems to be conserved in the
higher primates. We suggest that the originally described and the recently
discovered forms of CpG MTase be named dnmt1-a and dnmt1-b, respectively. T
he evolutionary and biological implications of this finding are discussed i
n relation to the cellular functions of the CpG residues and the CpG MTases
.