The paternal methylation imprint of the mouse H19 locus is acquired in thegonocyte stage during foetal testis development

Background: Germline-specific differential DNA methylation that persists th rough fertilization acid embryonic development is thought to be the 'imprin t' distinguishing the parental alleles of imprinted genes. If such methylat ion is to work as the imprinting mechanism, however, it has to be reprogram med following each passage through the germline. Previous studies on matern ally methylated genes have shown that their methylation imprints are first erased in primordial germ cells (PGCs) and then re-established during oocyt e growth. Results: We have examined the timing of the reprogramming of the paternal m ethylation imprint of the mouse H19 gene during germ cell development. In b oth male and female PGCs, the paternal allele is partially methylated where as the maternal allele is unmethylated. This partial methylation is complet ely erased in the female germline by entry into meiosis, establishing the o ocyte methylation pattern. In the male germline, both alleles become methyl ated, mainly during the gonocyte stage, establishing the sperm methylation pattern. Conclusion: The paternal methylation imprint of H19 is established in the m ale germline and erased in the female germline at specific developmental st ages. The identification of the timings of the methylation and demethylatio n should help to identify and characterize the biochemical basis of the rep rogramming of imprinting.