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首页> 外文期刊>Molecular and Cellular Biology >An Antisense RNA Regulates the Bidirectional Silencing Property of the Kcnq1 Imprinting Control Region
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An Antisense RNA Regulates the Bidirectional Silencing Property of the Kcnq1 Imprinting Control Region

机译：反义RNA调节Kcnq1印迹控制区域的双向沉默特性。

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摘要

The Kcnq1 imprinting control region (ICR) located in intron 10 of the Kcnq1 gene is unmethylated on the paternal chromosome and methylated on the maternal chromosome and has been implicated in the manifestation of parent-of-origin-specific expression of six neighboring genes. The unmethylated Kcnq1 ICR harbors bidirectional silencer activity and drives expression of an antisense RNA, Kcnq1ot1, which overlaps the Kcnq1 coding region. To elucidate whether the Kcnq1ot1 RNA plays a role in the bidirectional silencing activity of the Kcnq1 ICR, we have characterized factor binding sites by genomic footprinting and tested the functional consequence of various deletions of these binding sites in an episome-based system. Deletion of the elements necessary for Kcnq1ot1 promoter function resulted in the loss of silencing activity. Furthermore, interruption of Kcnq1ot1 RNA production by the insertion of a polyadenylation sequence downstream of the promoter also caused a loss of both silencing activity and methylation spreading. Thus, the antisense RNA plays a key role in the silencing function of the ICR. Double-stranded RNA (dsRNA)-mediated RNA interference is unlikely to be involved, as the ICR is active irrespective of the simultaneous production of dsRNA from the genes it silences.
机译：位于 Kcnq1 基因内含子10的 Kcnq1 印迹控制区（ICR）在父本染色体上未甲基化，而在母本染色体上甲基化，并与六个相邻基因的母体特异性表达。未甲基化的 Kcnq1 ICR具有双向沉默子活性，并驱动与 Kcnq1 编码区重叠的反义RNA Kcnq1ot1 的表达。为了阐明 Kcnq1ot1 RNA是否在 Kcnq1 ICR的双向沉默活性中发挥作用，我们通过基因组足迹分析了因子结合位点，并测试了各种缺失的功能结果基于游离体的系统中的这些结合位点。 Kcnq1ot1 启动子功能所必需的元素的删除导致沉默活性的丧失。此外，通过在启动子下游插入聚腺苷酸化序列来中断 Kcnq1ot1 RNA的产生，也导致沉默活性和甲基化扩散的损失。因此，反义RNA在ICR的沉默功能中起关键作用。双链RNA（dsRNA）介导的RNA干扰不太可能涉及，因为ICR活跃，而与它沉默的基因同时产生dsRNA无关。

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