Retrotransposon silencing by DNA methylation can drive mammalian genomic imprinting.
Retrotransposon silencing by DNA methylation can drive mammalian genomic imprinting.
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DOI：
10.1371/journal.pgen.0030055
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发表时间：
2007-04-13
期刊：
影响因子：
4.5
通讯作者：
Kaneko-Ishino T
中科院分区：
文献类型：
--
作者：
Suzuki S;Ono R;Narita T;Pask AJ;Shaw G;Wang C;Kohda T;Alsop AE;Marshall Graves JA;Kohara Y;Ishino F;Renfree MB;Kaneko-Ishino T
在哺乳动物中，只有真兽目动物和有袋类动物是胎生的，并具有基因组印记，导致父母的起源特异性差异基因表达。我们采用比较分析的方法来研究哺乳动物基因组印记的起源。PEG 10（父系表达10）是一种逆转录转座子衍生的印迹基因，对小鼠胎盘的形成具有重要作用。在这里，我们表明，PEG 10的直向同源物存在于另一个兽目哺乳动物，有袋类tammar袋鼠（Macropus eugenii），但不是在一个原始的哺乳动物，产卵鸭嘴兽（Ornithorhynchus anatinus），这表明其密切的关系，在兽目哺乳动物的胎盘的起源。我们已经发现了一个迄今为止缺失的真兽目动物和有袋类动物之间的印记机制，因为tammar PEG 10是第一个与有袋类动物基因组印记相关的差异甲基化区域（DMR）的例子。令人惊讶的是，有袋类DMR严格限制在PEG 10的5′区域，而不像真兽类DMR，它覆盖了PEG 10和相邻印记基因SGCE的启动子区域。这些结果不仅证明了一个共同的起源的DMR相关的印记机制在兽类哺乳动物，但提供了第一个证明，DMR相关的基因组印记在真兽类可以起源于外源DNA序列和/或逆转录转座子的DNA甲基化的抑制。基因组印记是一种基因调控机制，控制基因的亲本来源依赖性表达。在真兽目动物中，印记对于胎儿和胎盘的发育是必不可少的，这种机制的缺陷是几种遗传疾病的原因。在真兽目哺乳动物中，基因组印记由DNA的差异甲基化控制。然而，没有这样的甲基化依赖机制已被确定与有袋动物的印记。通过比较所有三个现存类别的哺乳动物（真兽目，有袋目和单孔目动物）的基因组，我们研究了PEG 10（父系表达10）的进化，这是一种逆转录转座子衍生的印迹基因，对小鼠胎盘的形成至关重要。PEG 10存在于有袋类动物tammar wallaby中，但不存在于产卵的单孔目动物鸭嘴兽中。因此，PEG 10是在哺乳动物胎盘和胎生进化的时候被插入基因组的。这项研究表明，PEG 10不仅在有袋动物中有印记，而且其印记受到差异甲基化的调节，这表明甲基化在兽类祖先中有一个共同的起源。这些结果为反转录转座子插入能够驱动哺乳动物基因组印记的进化提供了直接证据。
Among mammals, only eutherians and marsupials are viviparous and have genomic imprinting that leads to parent-of-origin-specific differential gene expression. We used comparative analysis to investigate the origin of genomic imprinting in mammals. PEG10 (paternally expressed 10) is a retrotransposon-derived imprinted gene that has an essential role for the formation of the placenta of the mouse. Here, we show that an orthologue of PEG10 exists in another therian mammal, the marsupial tammar wallaby (Macropus eugenii), but not in a prototherian mammal, the egg-laying platypus (Ornithorhynchus anatinus), suggesting its close relationship to the origin of placentation in therian mammals. We have discovered a hitherto missing link of the imprinting mechanism between eutherians and marsupials because tammar PEG10 is the first example of a differentially methylated region (DMR) associated with genomic imprinting in marsupials. Surprisingly, the marsupial DMR was strictly limited to the 5′ region of PEG10, unlike the eutherian DMR, which covers the promoter regions of both PEG10 and the adjacent imprinted gene SGCE. These results not only demonstrate a common origin of the DMR-associated imprinting mechanism in therian mammals but provide the first demonstration that DMR-associated genomic imprinting in eutherians can originate from the repression of exogenous DNA sequences and/or retrotransposons by DNA methylation. Genomic imprinting is a gene regulatory mechanism controlling parent-of-origin-dependent expression of genes. In eutherians, imprinting is essential for fetal and placental development and defects in this mechanism are the cause of several genetic disorders. In eutherian mammals, genomic imprinting is controlled by differential methylation of the DNA. However, no such methylation-dependent mechanism had been previously identified in association with marsupial imprinting. By comparing the genome of all three extant classes of mammals (eutherians, marsupials, and monotremes), we have investigated the evolution of PEG10 (paternally expressed 10), a retrotransposon-derived imprinted gene that is essential for the formation of the placenta in the mouse. PEG10 was present in a marsupial species, the tammar wallaby, but absent from an egg-laying monotreme species, the platypus. Therefore, PEG10 was inserted into the genome at the time when the placenta and viviparity were evolving in therian mammals. This study has shown that PEG10 is not only imprinted in a marsupial, but that its imprint is regulated by differential methylation, suggesting a common origin for methylation in the therian ancestor. These results provide direct evidence that retrotransposon insertion can drive the evolution of genomic imprinting in mammals.
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