Sazhenova E A, Skriabin N A, Sukhanova N N, Lebedev I N
Mol Biol (Mosk). 2012 Mar-Apr;46(2):204-13.
Genomic imprinting is one of the most significant epigenetic phenomena, which is involved in the support of eutherians and human embryo development. Molecular mechanisms of imprinting disturbance in the pathology of pre- and postnatal ontogeny are related to a considerable degree to aberrant DNA methylation of imprinted genes. At present time data about multiple abnormalities of DNA methylation arising simultaneously in several imprinted loci are accumulated. This fact brings up the problem of interpretation of imprintome structural and functional organization, as well as interaction of imprinted genes. At present study DNA methylation analysis of 51 imprinted genes in placental tissues of human spontaneous abortions was performed. The presence of several epimutations affected from four to 12 imprinted genes was observed in each embryo. Majority of epimutations (78%) had a postzygotic origin. It was shown for the first time that the total incidence of abnormal DNA methylation of maternal and paternal alleles of imprinted genes, which lead to suppression of embryo development, is significantly higher than the incidence of epimutations, which can lead to stimulation of ontogenesis processes. This fact supports at the epigenetic level the "sex conflict" hypothesis, which explains the appearance of monoallelic imprinted genes expression in the evolution of mammals.
基因组印记是最重要的表观遗传现象之一,它参与了真兽类动物和人类胚胎的发育过程。产前和产后个体发育病理学中印记紊乱的分子机制在很大程度上与印记基因的异常DNA甲基化有关。目前,关于多个印记位点同时出现的DNA甲基化多重异常的数据正在积累。这一事实提出了印记组结构和功能组织的解释问题,以及印记基因之间的相互作用问题。在目前的研究中,对人类自然流产胎盘组织中的51个印记基因进行了DNA甲基化分析。在每个胚胎中都观察到了影响4到12个印记基因的几种表观突变。大多数表观突变(78%)起源于合子后。首次表明,导致胚胎发育受抑制的印记基因母本和父本等位基因异常DNA甲基化的总发生率显著高于可能导致个体发育过程受刺激的表观突变发生率。这一事实在表观遗传水平上支持了“性别冲突”假说,该假说解释了单等位基因印记基因表达在哺乳动物进化过程中的出现。