EXPRESSION OF H19 AND IGF2 GENES IN UNIPARENTAL MOUSE ES CELLS DURINGIN-VITRO AND IN-VIVO DIFFERENTIATION

Genomic imprinting is a process that results in the differential expre ssion of genes according to their parental inheritance. Two imprinted genes, insulin-like growth factor 2 (Igf2) and H19 are closely linked on mouse chromosome 7, and are expressed from the paternal and materna l alleles, respectively. The genes show striking similarity in their t issue-specific expression patterns, which led to the proposal that the ir transcription is controlled by a common regulatory domain that enab les only one gene to be active from each chromosome. Evidence is accum ulating, however, that the expression of H19 and Igf2 genes is not alw ays from their respective maternal and paternal alleles. This suggests that their expression is regulated independently of imprinting in som e tissues and teratomas. We have analysed the extent of non-imprinted expression of H19 and Igf2 in uniparental mouse embryonic stem (ES) ce lls during in vitro differentiation, and differentiation in teratomas using Northern blot and in situ hybridisation analysis. The expression patterns observed indicate that bath imprinting and non-imprinting me chanisms regulate transcription of these genes. Expression of one or t he other gene was observed in certain cell types in differentiated cul tures and in teratomas, suggesting that imprinting regulates the expre ssion of H19 and Igf2 genes in some differentiating cell lineages. At the same time, in other subpopulations of cells, co-expression of both genes was observed, demonstrating that the expression of these genes is not always regulated by genomic imprinting.