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首页> 外文期刊>Nature >Location of enhancers is essential for the imprinting of H19 and Igf2 genes.
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Location of enhancers is essential for the imprinting of H19 and Igf2 genes.

机译：增强子的位置对于印迹H19和Igf2基因至关重要。

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摘要

Genomic imprinting is the process in mammals by which gamete-specific epigenetic modifications establish the differential expression of the two alleles of a gene. The tightly linked H19 and Igf2 genes are expressed in tissues of endodermal and mesodermal origin, with H19 expressed from the maternal chromosome and Igf2 expressed from the paternal chromosome. A model has been proposed to explain the reciprocal imprinting of these genes; in this model, expression of the genes is governed by competition between their promoters for a common set of enhancers. An extra set of enhancers might be predicted to relieve the competition, thereby eliminating imprinting. Here we tested this prediction by generating mice with a duplication of the endoderm-specific enhancers. The normally silent Igf2 gene on the maternal chromosome was expressed in liver, consistent with relief from competition. We then generated a maternal chromosome containing a single set of enhancers located equidistant from 1gf2 and H19; the direction of the imprint was reversed. Thus, the location of the enhancers determines the outcome of competition in liver, and the strength of the H19 promoter is not sufficient to silence Igf2.
机译：基因组印迹是哺乳动物体内配子特异性表观遗传修饰建立基因两个等位基因差异表达的过程。紧密连接的H19和Igf2基因在内胚层和中胚层来源的组织中表达，其中H19从母本染色体表达，而Igf2从父本染色体表达。已经提出了一个模型来解释这些基因的相互印记。在该模型中，基因的表达受其启动子之间竞争一组共同的增强子的控制。可以预期会有一组额外的增强剂来减轻竞争，从而消除烙印。在这里，我们通过产生具有内胚层特异性增强子重复的小鼠来测试这种预测。母体染色体上通常沉默的Igf2基因在肝脏中表达，这与竞争的缓解相一致。然后，我们生成了一个母系染色体，其中包含一组与1gf2和H19等距的增强子。烙印的方向颠倒了。因此，增强子的位置决定了肝脏竞争的结果，H19启动子的强度不足以使Igf2沉默。

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