GSE185574
Rat and mouse imprintomes (allele-specific transcriptomes)
The rat is a widely used model for human physiology and psychology. However, due to their longer gestation periods and husbandry costs relative to mice, as well as the availability of superior molecular techniques to manipulate the mouse genome, relatively few genome-wide studies have been conducted in the rat. As such, a comprehensive analysis of genomic imprinting, which impacts complex traits such as growth and behaviour, has yet to be conducted in the rat. Towards this end, we systematically profiled embryonic and extra-embryonic tissue gene expression and DNA methylation with allele-specific resolution. We identified 14 embryonic and 26 extra-embryonic imprinted genes in the rat. Comparative analyses with mouse revealed that orthologous imprinted gene expression and associated canonical DNA methylation imprints are conserved in the embryo proper of the Muridae family. However, only 3 paternally expressed imprinted genes in the extra-embryonic embryo are conserved in Muridae, all of which are associated with non-canonical H3K27me3 imprints. The discovery of 8 novel candidate non-canonical imprinted genes unique to the rat is consistent with more rapid evolution of extra-embryonic imprinting. Cross-species analysis of novel rat imprinted genes with mouse and human revealed multiple mechanisms by which species-specific imprinted expression may be established, including H3K27me3 deposition in the oocyte, the birth of ZFP57 binding motifs and the insertion of endogenous retroviral promoters. Thus, characterization of the rat imprintome provides insights into the conservation of imprinted gene expression and the etiology of species-specific imprinting. Overall design: Strand-specific RNA-seq of epiblasts (EBs) and ectoplacental cones (EPCs) from rat and mouse embryos.