A screen for retrotransposed imprinted genes reveals an association between X chromosome homology and maternal germ-line methylation.
A screen for retrotransposed imprinted genes reveals an association between X chromosome homology and maternal germ-line methylation.
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DOI：
10.1371/journal.pgen.0030020
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发表时间：
2007-02-09
期刊：
影响因子：
4.5
通讯作者：
Oakey RJ
中科院分区：
文献类型：
--
作者：
Wood AJ;Roberts RG;Monk D;Moore GE;Schulz R;Oakey RJ
印记基因在配子发生过程中会发生表观遗传修饰，导致母系或父系来源的等位基因在后代中的转录沉默。以前的工作表明，印记和反转录转座的产品之间的关联，但这种联系的性质是没有很好地定义。在小鼠中，已经描述了三种印迹基因，它们起源于反转录转座和重叠的CpG岛，这些CpG岛在卵子发生期间经历甲基化。Nap 1 l5、U2 af 1-rs 1和Inpp5f_v2可能编码蛋白质，并共享两个额外的遗传特性：它们位于宿主转录本的内含子内，并来自X染色体上的亲本基因。单独使用这些序列特征，我们确定了Mcts 2，一种新的候选小鼠2号染色体上的印记逆转录基因。mcts 2已被证实为印记，证明它是父系表达，并在卵子发生过程中经历启动子甲基化。正向人类逆转录基因NAP 1 L5、INPP5F_V2和MCTS 2也显示为父系表达，从而描绘了人类染色体4、10和20上的新印迹基因座。印记和X染色体起源之间的显着相关性表明，与X染色体同源的逆转录转座元件可以在哺乳动物卵子发生过程中选择性地进行甲基化。传统的观点是，DNA携带着我们所有的遗传信息，我们的基因控制着成年期的发育。表观遗传学是一个术语，用来描述那些不是由DNA序列编码的效应，但仍然可以影响我们的发展和福祉，它的发现为我们对遗传学的理解增加了另一层复杂性。受表观遗传控制的一类基因是印记基因。哺乳动物的每个基因都有两个拷贝，一个来自母亲，一个来自父亲，在大多数情况下，两者都是活跃的。然而，对于哺乳动物中的少数印记基因，只有一个是活跃的，无论是母亲或父亲的副本。表观遗传学相当于一个控制系统，用于适当地打开和关闭基因。我们专注于一组很少研究的印记基因，这些基因的共同特征为它们的进化起源提供了线索。这些所谓的“逆转录基因”是DNA的蛋白质编码序列，它们经历了复制并跳跃到基因组中的新位置。正因为如此，才有可能确定许多印记逆转录基因起源于何处以及大致的时间。这为研究哺乳动物进化过程中产生印记基因的分子事件提供了机会。
Imprinted genes undergo epigenetic modifications during gametogenesis, which lead to transcriptional silencing of either the maternally or the paternally derived allele in the subsequent generation. Previous work has suggested an association between imprinting and the products of retrotransposition, but the nature of this link is not well defined. In the mouse, three imprinted genes have been described that originated by retrotransposition and overlap CpG islands which undergo methylation during oogenesis. Nap1l5, U2af1-rs1, and Inpp5f_v2 are likely to encode proteins and share two additional genetic properties: they are located within introns of host transcripts and are derived from parental genes on the X chromosome. Using these sequence features alone, we identified Mcts2, a novel candidate imprinted retrogene on mouse Chromosome 2. Mcts2 has been validated as imprinted by demonstrating that it is paternally expressed and undergoes promoter methylation during oogenesis. The orthologous human retrogenes NAP1L5, INPP5F_V2, and MCTS2 are also shown to be paternally expressed, thus delineating novel imprinted loci on human Chromosomes 4, 10, and 20. The striking correlation between imprinting and X chromosome provenance suggests that retrotransposed elements with homology to the X chromosome can be selectively targeted for methylation during mammalian oogenesis. The conventional view is that DNA carries all of our heritable information and our genes control development into adulthood. The discovery of epigenetics, a term coined to describe effects that are not coded for by DNA sequence, but can nonetheless affect our development and well-being, has added another layer of complexity to our understanding of genetics. One class of genes under epigenetic control are imprinted genes. Mammals inherit two copies of every gene, one from mother and one from father, and in most cases, both are active. However, for a small number of imprinted genes in mammals, only one is active, either the maternal or the paternal copy. Epigenetics amounts to a control system for switching genes on and off appropriately. We focus on a group of little-studied imprinted genes that share features that give clues to their evolutionary origins. These so-called “retrogenes” are protein-coding sequences of DNA that have undergone duplication and jumped into novel locations in the genome. Because of this, it is possible to determine where, and roughly when, many of the imprinted retrogenes originated. This provides an opportunity to study the molecular events that have generated imprinted genes during mammalian evolution.
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