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首页> 外文期刊>Human Molecular Genetics >Ftx is a non-coding RNA which affects Xist expression and chromatin structure within the X-inactivation center region.
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Ftx is a non-coding RNA which affects Xist expression and chromatin structure within the X-inactivation center region.

机译：Ftx是一种非编码RNA，会影响X灭活中心区域内的Xist表达和染色质结构。

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摘要

X chromosome inactivation (XCI) is an essential epigenetic process which involves several non-coding RNAs (ncRNAs), including Xist, the master regulator of X-inactivation initiation. Xist is flanked in its 5' region by a large heterochromatic hotspot, which contains several transcription units including a gene of unknown function, Ftx (five prime to Xist). In this article, we describe the characterization and functional analysis of murine Ftx. We present evidence that Ftx produces a conserved functional long ncRNA, and additionally hosts microRNAs (miR) in its introns. Strikingly, Ftx partially escapes X-inactivation and is upregulated specifically in female ES cells at the onset of X-inactivation, an expression profile which closely follows that of Xist. We generated Ftx null ES cells to address the function of this gene. In these cells, only local changes in chromatin marks are detected within the hotspot, indicating that Ftx is not involved in the global maintenance of the heterochromatic structure of this region. The Ftx mutation, however, results in widespread alteration of transcript levels within the X-inactivation center (Xic) and particularly important decreases in Xist RNA levels, which were correlated with increased DNA methylation at the Xist CpG island. Altogether our results indicate that Ftx is a positive regulator of Xist and lead us to propose that Ftx is a novel ncRNA involved in XCI.
机译：X染色体失活（XCI）是必不可少的表观遗传过程，涉及多个非编码RNA（ncRNA），包括Xist，它是X失活起始的主要调控因子。 Xist在其5'区域的两侧是一个大的异色热点，该热点包含多个转录单元，其中包括功能未知的基因Ftx（Xist的五个引物）。在本文中，我们描述了小鼠Ftx的表征和功能分析。我们目前的证据，Ftx产生一个保守的功能长ncRNA，并在其内含子中另外存在microRNA（miR）。引人注目的是，Ftx部分逃脱了X灭活，并在X灭活开始时特别在雌性ES细胞中被上调，其表达特征紧随Xist。我们生成了Ftx null ES细胞来解决该基因的功能。在这些细胞中，仅在热点内检测到染色质标记的局部变化，表明Ftx不参与该区域异色结构的整体维持。但是，Ftx突变会导致X灭活中心（Xic）内的转录物水平发生广泛变化，尤其是Xist RNA水平的下降尤为重要，这与Xist CpG岛的DNA甲基化增加有关。总的来说，我们的结果表明Ftx是Xist的正调控因子，并导致我们提出Ftx是XCI中涉及的新型ncRNA。

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