THE ONTOGENY OF ALLELE-SPECIFIC METHYLATION ASSOCIATED WITH IMPRINTEDGENES IN THE MOUSE

We have investigated the DNA methylation patterns in genomically impri nted genes of the mouse. Both Igf2 and H19 are associated with clear-c ut regions of allele-specific paternal modification in late embryonic and adult tissues. By using a sensitive PCR assay, it was possible to follow the methylation state of individual HpaII sites in these genes through gametogenesis and embryogenesis. Most of these CpG moieties ar e not differentially modified in the mature gametes and also become to tally demethylated in the early embryo in a manner similar to non-impr inted endogenous genes. Thus, the overall allele-specific methylation pattern at these sites must be established tater during embryogenesis after the blastula stage. In contrast, sites in an Igf2r gene intron a nd one CpG residue in the Igf2 upstream region have allele-specific mo dification patterns which are established either in the gametes or sho rtly after fertilization and are preserved throughout pre-implantation embryogenesis. These studies suggest that only a few DNA modification s at selective positions in imprinted genes may be candidates for play ing a rote in the maintenance of parental identity during development.