COMPARATIVE-ANALYSIS OF IGF-2 H19 IMPRINTED DOMAIN - IDENTIFICATION OF A HIGHLY CONSERVED INTERGENIC DNASE-I HYPERSENSITIVE REGION

The closely linked, reciprocally imprinted mouse genes, insulin-like g rowth factor II (Igf-2) and H19, provide a significant paradigm for st udies of the mechanism of parental imprinting. Most studies have focus ed on regions within and proximate to the genes, but an analysis of th e whole region is essential to unravel how expression of these genes i s controlled. A comparative long-range analysis of a 130-kb genomic re gion containing both genes was therefore carried out using material fr om normal and chromosome 7 maternal uniparental disomic embryos. We ex amined DNA methylation, chromatin structure assessed by hypersensitivi ty to DNase I, and regions that show strong conservation among mammali an species. The critical boundaries of differential DNA methylation an d DNase I hypersensitivity are apparently confined within and proximat e to the Igf-2 and H19 genes. However, we have identified a novel inte rgenic region that is conserved in mammals, GC-rich, and unmethylated in embryos and contains major DNase I hypersensitive sites. (C) 1994 A cademic Press, Inc.