Mann J R, Szabó P E, Reed M R, Singer-Sam J
Division of Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010-3011, USA.
Crit Rev Eukaryot Gene Expr. 2000;10(3-4):241-57. doi: 10.1615/critreveukargeneexpr.v10.i3-4.30.
Genomic imprinting is a special form of epigenetic system that determines the parent-of-origin-specific, or monoallelic, expression of a small number of genes, termed "imprinted" genes. Considerable sequence and methylation analysis of imprinted genes has revealed a common theme: Regions of allele-specific methylation inherited from the gametes, or primary differentially methylated regions (DMRs), are associated with CpG islands and repeat elements, and this overall structure suggests functional significance. For at least three imprinted genes the sequence of the primary DMR constitutes an element able to regulate gene activity in cis--a chromatin insulator and a promoter of an antisense transcript. In these cases the unique feature of imprinting appears to be in the ability to switch the regulatory capacity of these elements on or off by the absence or presence of inherited methylation. Increasing evidence therefore suggests that genomic imprinting for at least some genes constitutes the regulation of gene regulatory elements by methylation. An important challenge now is to determine how the differential methylation of primary DMR sequences is established in the germ line. If methylation is the primary imprint, then the processes establishing it are the primary imprinting mechanisms. Trans-acting factors that are expressed in one sex of germ line and not the other are likely to be involved, and their ability to methylate may be mediated through repeat elements associated with the sequence of primary DMRs.
基因组印记是一种特殊形式的表观遗传系统，它决定了少数被称为“印记”基因的亲本来源特异性或单等位基因表达。对印记基因进行的大量序列和甲基化分析揭示了一个共同的主题：从配子继承而来的等位基因特异性甲基化区域，即主要差异甲基化区域（DMRs），与CpG岛和重复元件相关，并且这种整体结构暗示了其功能意义。对于至少三个印记基因而言，主要DMR的序列构成了一个能够顺式调节基因活性的元件——一种染色质绝缘子和一个反义转录本的启动子。在这些情况下，印记的独特特征似乎在于能够通过遗传甲基化的缺失或存在来开启或关闭这些元件的调节能力。因此，越来越多的证据表明，至少某些基因的基因组印记是通过甲基化对基因调控元件进行的调节。现在一个重要的挑战是确定主要DMR序列的差异甲基化是如何在生殖系中建立的。如果甲基化是主要印记，那么建立它的过程就是主要的印记机制。在一种性别的生殖系中表达而在另一种性别的生殖系中不表达的反式作用因子可能会参与其中，并且它们的甲基化能力可能是通过与主要DMR序列相关的重复元件介导的。
