Asynchronous replication of imprinted genes is established in the gametes and maintained during development

Genomic imprinting is characterized by allele-specific expression of multip le genes within large chromosomal domains' that undergo DNA replication asy nchronously during S phase(2,3). Here we show, using both fluorescence in s itu hybridization analysis and S-phase fractionation techniques, that diffe rential replication timing is associated with imprinted genes in a variety of fell types, and is already present in the pre-implantation embryo soon a fter fertilization. This pattern is erased before meiosis in the germ line, and parent-specific replication timing is then reset in late gametogenesis in both the male and female. Thus, asynchronous replication timing is esta blished in the gametes and maintained throughout development, indicating th at it may function as a primary epigenetic marker for distinguishing betwee n the parental alleles.