Koide T, Ainscough J, Wijgerde M, Surani M A
Wellcome/CRC Institute of Cancer and Developmental Biology, Cambridge, United Kingdom.
Genomics. 1994 Nov 1;24(1):1-8. doi: 10.1006/geno.1994.1574.
The closely linked, reciprocally imprinted mouse genes, insulin-like growth factor II (Igf-2) and H19, provide a significant paradigm for studies of the mechanism of parental imprinting. Most studies have focused on regions within and proximate to the genes, but an analysis of the whole region is essential to unravel how expression of these genes is controlled. A comparative long-range analysis of a 130-kb genomic region containing both genes was therefore carried out using material from normal and chromosome 7 maternal uniparental disomic embryos. We examined DNA methylation, chromatin structure assessed by hypersensitivity to DNase I, and regions that show strong conservation among mammalian species. The critical boundaries of differential DNA methylation and DNase I hypersensitivity are apparently confined within and proximate to the Igf-2 and H19 genes. However, we have identified a novel intergenic region that is conserved in mammals, GC-rich, and unmethylated in embryos and contains major DNase I hypersensitive sites.
紧密连锁、相互印记的小鼠基因胰岛素样生长因子II（Igf-2）和H19，为亲本印记机制的研究提供了一个重要范例。大多数研究集中在基因内部及附近区域，但对整个区域进行分析对于阐明这些基因的表达调控方式至关重要。因此，我们利用正常胚胎和7号染色体单亲二体胚胎的材料，对包含这两个基因的130 kb基因组区域进行了比较性的长程分析。我们检测了DNA甲基化、通过对DNase I的敏感性评估的染色质结构，以及在哺乳动物物种间表现出高度保守性的区域。DNA甲基化差异和DNase I超敏反应的关键边界显然局限于Igf-2和H19基因内部及附近。然而，我们发现了一个在哺乳动物中保守、富含GC、在胚胎中未甲基化且包含主要DNase I超敏位点的新型基因间区域。
