Birger Y, Shemer R, Perk J, Razin A
Department of Cellular Biochemistry, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
Nature. 1999 Jan 7;397(6714):84-8. doi: 10.1038/16291.
Genomic imprinting is a phenomenon characterized by parent-of-origin-specific expression. The imprint is a mark established during germ-cell development to distinguish between the paternal and maternal copies of the imprinted genes. This imprint is maintained throughout embryo development and erased in the embryonic gonads to set the stage for a new imprint. DNA methylation is essential in this process as shown by the presence of differentially methylated regions (DMRs) in all imprinted genes and by the loss of imprinting in mice that are deficient in DNA methylation or upon deletion of DMRs. Here we show that a DMR in the imprinted Igf2r gene (which encodes the receptor for insulin-like growth factor type-2) that has been shown to be necessary for imprinting includes a 113-base-pair sequence that constitutes a methylation imprinting box. We identify two new cis-acting elements in this box that bind specific proteins: a de novo methylation signal and an allele-discrimination signal. We propose that this regulatory system, which we show to be involved in the establishment of differential methylation in the Igf2r DMR, represents a critical element in the imprinting process.
基因组印记是一种以亲本来源特异性表达为特征的现象。印记是在生殖细胞发育过程中建立的一种标记，用于区分印记基因的父本和母本拷贝。这种印记在胚胎发育过程中一直保持，并在胚胎性腺中被擦除以为新的印记奠定基础。正如所有印记基因中存在差异甲基化区域（DMR）以及DNA甲基化缺陷或DMR缺失的小鼠中印记丢失所表明的那样，DNA甲基化在这一过程中至关重要。在此我们表明，印记的Igf2r基因（编码胰岛素样生长因子2型受体）中的一个DMR对于印记是必需的，该DMR包含一个113个碱基对的序列，构成一个甲基化印记框。我们在这个框中鉴定出两个与特定蛋白质结合的新顺式作用元件：一个从头甲基化信号和一个等位基因区分信号。我们提出，这个我们证明参与Igf2r DMR中差异甲基化建立的调控系统，是印记过程中的一个关键要素。
