Mechanisms for methylation imprinting establishment afterfertilization

基因组印记是哺乳动物的一种表观遗传现象，其中一部分基因是单等位基因表达，这取决于它们的亲本来源。为了揭示H19-ICR序列中区分亲本起源及其沉积位点的表观遗传特征的身份，结果表明：1)父本H19-ICR的甲基化不依赖于其在精子中的建立；2)在着床前胚胎中，CTCF位点不需要建立父本等位基因特异性甲基化；3)甲基化印迹不需要与卵母细胞中小RNA序列相对应的H19-ICR序列；4)H19-ICR的差异甲基化是通过其父本等位基因特异性建立的5) H19-ICR中的Oct-sox基序在体内植入后具有抗甲基化保护活性。6)鸡HS4绝缘子对H19-ICR的差异DNA甲基化不具有保护作用。

enomic imprinting is an epigenetic phenomenon in mammals, in which a subset of genes are mono-allelically expressed depending on their parental origin.To reveal identity of the epigenetic signature discriminating the parental origin and its deposition site within the H19-ICR sequence, transgenic mouse methodology was employed and following findings were demonstrated:1) Paternal H19-ICR acquired methylation independently of its establishment in sperm2) CTCF sites were not required to establish paternal-allele-specific methylation in pre-implantation embryos3) Sequences in the H19-ICR corresponding to the small RNA sequences in oocytes were dispensable for methylation imprinting4) Differential methylation of the H19-ICR was established by its paternal-allele-specific methylation and maternal-allele-specific protection-against-methylation5) Oct-sox motif in the H19-ICR harbored protection-against-methylation activity in vivo after implantation6) Chicken HS4 insulator did not protect the H19-ICR from differential DNA methylation.