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.
May
Andreas
A
Institute for Human Genetics, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
Reifenberg
Kurt
K
Zechner
Ulrich
U
Haaf
Thomas
T
D000818:Animals; D002455:Cell Division / Q000235:genetics; D002478:Cells, Cultured; D002874:Chromosome Mapping; D002875:Chromosomes / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics*; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism*; D047108:Embryonic Development / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D005306:Fertilization / Q000235:genetics; D018392:Genomic Imprinting / Q000235:genetics*; D042822:Genomic Instability / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009028:Morula / Q000166:cytology / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics; D013997:Time Factors; D015533:Transcriptional Activation / Q000235:genetics; D015053:Zygote / Q000166:cytology / Q000378:metabolism
D022661:RNA, Untranslated