Genotype-Epigenotype Interaction at the IGF2 DMR.
Genotype-Epigenotype Interaction at the IGF2 DMR.
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DOI：
10.3390/genes6030777
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发表时间：
2015-08-28
期刊：
影响因子：
3.5
通讯作者：
Hoyo C
中科院分区：
文献类型：
--
作者：
Murphy SK;Erginer E;Huang Z;Visco Z;Hoyo C
父系表达的胰岛素样生长因子II（IGF2）编码一种基因，其蛋白产物作为一种有效的生长有丝分裂原发挥作用。IGF2的过表达与多种疾病和病症有关。IGF2部分受两个亲代衍生等位基因的差异甲基化调节。位于IGF2印迹启动子上游的差异甲基化区域（DMR）在环境压力下表现出可塑性，并在几种类型的癌症中低甲基化。通过亚硫酸氢盐焦磷酸测序和核苷酸测序的确认，我们发现了CpG到CpG的颠换，其导致构成该DMR的三个CpG之一的低甲基化。多态性的存在引入了遗传而不是环境驱动的低甲基化的表观遗传来源，其与非遗传来源相加。
Paternally expressed Insulin-like Growth Factor II (IGF2) encodes a gene whose protein product functions as a potent growth mitogen. Overexpression of IGF2 has been implicated in a wide number of disorders and diseases. IGF2 is regulated in part by differential methylation of the two parentally derived alleles. The differentially methylated region (DMR) located upstream of the imprinted promoters of IGF2 exhibits plasticity under environmental stress and is hypomethylated in several types of cancer. Through bisulfite pyrosequencing and confirmation by nucleotide sequencing, we discovered a CpG to CpC transversion that results in hypomethylation of one of the three CpGs comprising this DMR. The presence of the polymorphism introduces a genetic rather than an environmentally-driven epigenetic source of hypomethylation that is additive to non-genetic sources.