Novel splice variants associated with one of the zebrafish dnmt3 genes

DNA methylation and the methyltransferases are known to be important in vertebrate development and this may be particularly true for the Dnmt3 family of enzymes because they are thought to be the de novo methyltransferases. Mammals have three Dnmt3 genes; Dnmt3a, Dnmt3b, and Dnmt3L, two of which encode active enzymes and one of which produces an inactive but necessary cofactor. However, due to multiple promoter use and alternative splicing there are actually a number of dnmt3 isoforms present. Six different dnmt3 genes have recently been identified in zebrafish.

We have examined two of the dnmt3 genes in zebrafish that are located in close proximity in the same linkage group and we find that the two genes are more similar to each other than they are to the other zebrafish dnmt3 genes. We have found evidence for the existence of several different splice variants and alternative splice sites associated with one of the two genes and have examined the relative expression of these genes/variants in a number of zebrafish developmental stages and tissues.

The similarity of the dnmt3-1 and dnmt3-2 genes suggests that they arose due to a relatively recent gene duplication event. The presence of alternative splice and start sites, reminiscent of what is seen with the human DNMT3s, demonstrates strong parallels between the control/function of these genes across vertebrate species. The dynamic expression levels of these genes/variants suggest that they may well play a role in early development and this is particularly true for dnmt3-2-1 and dnmt3-1. dnmt3-2-1 is the predominantly expressed form prior to zygotic gene activation whereas dnmt3-1 predominates post zygotic gene activation suggesting a distinct developmental role for each.