Genomic imprinting in the post-natal marsupial (#257)
Genomic imprinting is a rare epigenetic mechanism that results in parental specific monoallelic expression. Several genes that regulate nutrition and growth of the developing mammalian fetus have been identified as imprinted in both the eutherian and marsupial placenta. Two of these genes are insulin (INS) and insulin-like growth factor 2 (IGF2). Both INS and IGF2 are important for the initiation and maintenance of lactation. We examined whether these genes also show monoallelic expression in the mammary gland, a site comparable to the placenta for the growth and development of the young. We used a marsupial model as growth and development of the young occurs post-natally, supported by a complex and extended period of lactation. Thus there may be a greater selection for imprinting to regulate postnatal development in the marsupial compared to its prenatal development.
Direct sequencing confirmed that both INS and IGF2 were imprinted in a tissue specific manner in the tammar pouch young liver and were monoallelically expressed in the mammary gland. INS 5´RACE using mammary gland and liver RNA identified an alternate transcription start site (TSS) to the one used in the pancreas. This TSS was located in the second to last exon of the tyrosine hydroxylase (TH) gene and produced a novel TH-INS chimera. Bisulphite sequencing showed that the INS TSS was highly methylated, but that it did not differ between parental alleles, whereas the TH-INS TSS appeared to be a putative differentially methylated region (DMR). This is the first study to identify INS imprinting outside the yolk sac and suggests that genomic imprinting could regulate growth and development of the post-natal young. These results support the maternal-infant co-adaptation hypothesis and suggest that imprinting in the mammary gland may be as critical for post-natal survival in mammals as it is in the placenta for pre-natal development.