Hark A T, Tilghman S M
Howard Hughes Medical Institute and Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Hum Mol Genet. 1998 Nov;7(12):1979-85. doi: 10.1093/hmg/7.12.1979.
Genomic imprinting in mammals is an epigenetic process that results in differential expression of the two parental alleles. The tightly linked murine H19 and Igf2 genes are reciprocally imprinted: H19 is expressed from the maternal chromosome while Igf2 is expressed from the paternal chromosome. A single regulatory region in the 5' flank of the H19 gene has been implicated in silencing both genes. On the paternal chromosome, this region is heavily methylated at CpG residues, leading to repression of the H19 gene. The mechanism by which the same region in an unmethylated state on the maternal chromosome silences Igf2 is less well understood. We have probed the chromatin structure of the region by assessing its sensitivity to nuclease digestion. Two regions of nuclease hypersensitivity that are specific to the maternal chromosome were identified. These coincide with the region that is most heavily methylated on the paternal chromosome. As is the case with paternal methylation, hypersensitivity is present in all tissues surveyed, irrespective of H19 expression. We suggest that the chromatin structure of the maternal 5' flank of the H19 gene may represent an epigenetic mark involved in the silencing of Igf2.
哺乳动物中的基因组印记是一种表观遗传过程，导致两个亲本等位基因的差异表达。紧密连锁的小鼠H19和Igf2基因相互印记：H19从母本染色体表达，而Igf2从父本染色体表达。H19基因5'侧翼的一个单一调控区域与这两个基因的沉默有关。在父本染色体上，该区域在CpG残基处高度甲基化，导致H19基因受到抑制。母本染色体上处于未甲基化状态的同一区域使Igf2沉默的机制尚不太清楚。我们通过评估该区域对核酸酶消化的敏感性来探测其染色质结构。鉴定出了两个对母本染色体特异的核酸酶高敏区域。这些区域与父本染色体上甲基化程度最高的区域一致。与父本甲基化情况一样，在所调查的所有组织中均存在高敏性，与H19的表达无关。我们认为，H19基因母本5'侧翼的染色质结构可能代表一种参与Igf2沉默的表观遗传标记。
