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，其中一个基因子集根据其亲本来源而单等位地表达。为了揭示区分亲本来源及其在H19-ICR序列中的沉积位点的表观遗传标记的身份，采用转基因小鼠方法，并证明了以下结果：1）父源H19-ICR获得甲基化独立于其在精子中的建立2）CTCF位点不需要建立父源等位基因，3）H19-ICR中与卵母细胞中的小RNA序列相对应的序列进行甲基化印迹分析4）H19-ICR的差异甲基化是通过其父亲等位基因特异性甲基化和母亲等位基因特异性保护性抗甲基化来建立的5）H19-ICR中的Oct-sox基序具有保护性抗甲基化，6）鸡HS 4绝缘子不能保护H19-ICR免受差异DNA甲基化的影响。

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.