INSULATOR IN THE H19 IMPRINTING

Mammalian development requires the genomes from the maternal and the paternal side (McGrath and Solter 1984; Surani et al. 1984). Their genetic nonequivalence is mediated by genomic imprinting, an epigenetic mecha-nism resulting in a parent-of-origin-dependent expression of a small number of genes (Tilghman 1999). The best studied pair of imprinted genes are H19 and Igf2, two closely linked, oppositely imprinted genes located on mouse chromosome 7. H19 is transcribed from the ma-ternally inherited allele (Bartolomei et al. 1991), whereas Igf2 is paternally expressed (DeChiara et al. 1991). The coordinated expression of H19 and Igf2 is controlled by two regulatory elements: a shared enhancer downstream of the H19 gene (Leighton et al. 1995), and an element re-ferred to as imprinting control region (ICR) located up-stream of the H19 gene (Fig. 1). Much attention has fo-cused on the H19 ICR as a key element in the regulation of monoallelic expression of H19 and Igf2, as its deletion results in activation of the normally silent H19 allele and a concomitant reduction in Igf2 expression upon paternal transmission, with a reciprocal effect upon maternal in-heritance of the deletion (Thorvaldsen et al. 1998)