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首页> 外文期刊>PLoS Genetics >Xist RNA repeat E is essential for ASH2L recruitment to the inactive X and regulates histone modifications and escape gene expression
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Xist RNA repeat E is essential for ASH2L recruitment to the inactive X and regulates histone modifications and escape gene expression

机译：Xist RNA重复E对ASH2L募集至非活性X至关重要，并调节组蛋白修饰和逃避基因表达

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摘要

Long non-coding RNA Xist plays a crucial role in establishing and maintaining X-chromosome inactivation (XCI) which is a paradigm of long non-coding RNA-mediated gene regulation. Xist has Xist-specific repeat elements A-F which are conserved among eutherian mammals, underscoring their functional importance. Here we report that Xist RNA repeat E, a conserved Xist repeat element in the Xist exon 7, interacts with ASH2L and contributes to maintenance of escape gene expression level on the inactive X-chromosome (Xi) during XCI. The Xist repeat E-deletion mutant female ES cells show the depletion of ASH2L from the Xi upon differentiation. Furthermore, a subset of escape genes exhibits unexpectedly higher expression in the repeat E mutant cells than the cells expressing wildtype Xist during X-inactivation, whereas the silencing of X-linked non-escape genes is not affected. We discuss the implications of these results to understand the role of ASH2L and Xist repeat E for histone modifications and escape gene regulation during random X-chromosome inactivation.
机译：长的非编码RNA Xist在建立和维持X染色体失活（XCI）中起着关键作用，XCI是长的非编码RNA介导的基因调控的范例。 Xist具有Xist特异的重复元件A-F，该元件在以太哺乳动物中是保守的，强调了它们的功能重要性。在这里我们报告Xist RNA重复E，Xist外显子7中的保守Xist重复元素，与ASH2L相互作用，并有助于XCI期间在非活性X染色体（Xi）上维持逃逸基因表达水平。 Xist重复E缺失突变雌性ES细胞在分化后显示出Xi的ASH2L耗竭。此外，在X灭活过程中，逃逸基因的一个子集在重复E突变细胞中比表达野生型Xist的细胞出乎意料地更高的表达，而X连锁的非逃逸基因的沉默却不受影响。我们讨论这些结果的含义，以了解ASH2L和Xist重复E在随机X染色体失活过程中对组蛋白修饰和逃逸基因调控的作用。

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