Mechanisms for methylation imprinting establishment afterfertilization

基因组印记是哺乳动物中的一种表观遗传现象，其中一部分基因的表达取决于其亲代来源。为了揭示区分亲本来源及其在H19-ICR序列中的沉积位置的表观遗传特征的同一性，利用转基因小鼠方法，证实了以下发现：1)父系H19-ICR获得了独立于精子的甲基化2)CTCF位点不需要在植入前胚胎中建立父系特异的甲基化3)与卵母细胞中的小RNA序列相对应的H19-ICR中的序列对于甲基化印迹是必要的4)H19-ICR的差异甲基化是通过其父系特有的甲基化和母系特有的等位基因保护来建立的5)植入后H19-ICR中的Oct-Sox基序具有防止甲基化的活性6)鸡4 HS4绝缘子不能保护H19-ICR免受DNA的差异甲基化。

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.