Asynchronous replication dynamics of imprinted and non-imprinted chromosome regions in early mouse embryos

We have used interphase FISH to analyze the replication behavior of four imprinted chromosome regions (Snrpn, Zim1-Peg3, Dlk1-Gtl2, and Igf2r) and five non-imprinted regions in mouse one-cell to morula-stage embryos and embryonic fibroblasts. In general, imprinted chromosome regions showed the expected asynchronous pattern of replication throughout all analyzed stages of preimplantation development and in differentiated cells. The Dlk1-Gtl2 locus which is not expressed and Igf2r which is biallelically expressed in early embryos showed a relaxation of replication asynchrony at the morula stage. Asynchronous replication in zygotes and two-cell embryos was not specific to imprinted regions. Three non-imprinted loci (Emp1-Pbp2-Dyntl1, Hbb-b1-Hbb-b2-Hbb-y, and Opa1) as well as one gene-free region on chromosome 7A1 switched from asynchronous replication in one- and two-cell embryos to synchronous replication in 4-cell embryos and later stages. Another gene-free region on chromosome 16C2 showed a more gradual transition from asynchronous to synchronous replication from two-cell to morula-stage embryos. We propose that replication asynchrony contributes to the striking asymmetry between the two parental genomes, which are epigenetically reprogrammed after fertilization into a diploid somatic genome. The switching of non-imprinted genes from asynchronous to synchronous replication may be associated with embryonic genome activation and restoration of transcriptional potential for somatic development.