Allele-specific replication timing of imprinted gene regions

Abstract

SEVERAL lines of evidence suggest that the paternal and maternal genomes may have different expression patterns in the developing organism1 and this has been confirmed by the identification of endogenous genes that are parentally imprinted in the mouse2–5. Little is known about the precise mechanisms involved in the process, but structural differences between the two alleles must somehow provide cis-acting signals for directing parental-specific transcription. Cell-cycle replication time is one parameter that has been shown to be associated with both tissue-specific gene expression6,7 and the allele-specific transcription patterns of the X chromosomes in female cells8. For this reason we have examined the replication timing patterns for the chromosomal regions containing the imprinted genes Igf2, Igf2r, H19 and Snrpn in the mouse. At all of these sites, and their corresponding positions in the human genome, the two homologous alleles replicate asynchronously and it is always the paternal allele that is early-replicating. Thus imprinted genes appear to be embedded in large DNA domains with differential replication patterns, which may provide a structural imprint for parental identity.