The H19 methylation imprint is erased and re-established differentially onthe parental alleles during male germ cell development

Differences in DNA methylation distinguish the maternal and paternal allele s of many imprinted genes, Allele specific methylation that is inherited fr om the gametes and maintained throughout development has been proposed as a candidate imprinting mark. To determine how methylation is established in the germline, we have analyzed the allelic methylation patterns of the mate rnally expressed, paternally methylated H19 gene during gametogenesis in th e mouse embryo. We show here that both parental alleles are devoid of methy lation in male and female mid-gestation embryonic germ cells, suggesting th at methylation imprints are erased in the germ cells prior to this time. In addition, we demonstrate that the subsequent hypermethylation of the pater nal and maternal alleles in the male germline occurs at different times, Al though the paternal allele becomes hypermethylated during fetal stages, met hylation of the maternal allele begins during perinatal stages;and continue s postnatally through the onset of meiosis, The? differential acquisition o f methylation on the parental H19 alleles during gametogenesis implies that the two unmethylated alleles can still be distinguished from each other, T hus, in the absence of DNA methylation, other epigenetic mechanism(s) appea r to maintain parental identity at the H19 locus during male germ cell deve lopment.