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LINE-1 活性在 X 染色体失活过程中形成兼性异染色质。

LINE-1 activity in facultative heterochromatin formation during X chromosome inactivation.

机构信息

Institut Curie, Paris F-75248, France.

出版信息

Cell. 2010 Jun 11;141(6):956-69. doi: 10.1016/j.cell.2010.04.042.

DOI:10.1016/j.cell.2010.04.042
PMID:20550932
Abstract

During X chromosome inactivation (XCI), Xist RNA coats and silences one of the two X chromosomes in female cells. Little is known about how XCI spreads across the chromosome, although LINE-1 elements have been proposed to play a role. Here we show that LINEs participate in creating a silent nuclear compartment into which genes become recruited. A subset of young LINE-1 elements, however, is expressed during XCI, rather than being silenced. We demonstrate that such LINE expression requires the specific heterochromatic state induced by Xist. These LINEs often lie within escape-prone regions of the X chromosome, but close to genes that are subject to XCI, and are associated with putative endo-siRNAs. LINEs may thus facilitate XCI at different levels, with silent LINEs participating in assembly of a heterochromatic nuclear compartment induced by Xist, and active LINEs participating in local propagation of XCI into regions that would otherwise be prone to escape.

摘要

在 X 染色体失活(XCI)过程中,Xist RNA 包裹并沉默女性细胞中两条 X 染色体中的一条。尽管已经提出 LINE-1 元件可能在其中发挥作用,但对于 XCI 如何在染色体上传播知之甚少。在这里,我们表明 LINE 参与创建一个沉默的核区,基因被招募到这个核区。然而,一小部分年轻的 LINE-1 元件在 XCI 期间表达,而不是被沉默。我们证明这种 LINE 表达需要 Xist 诱导的特定异染色质状态。这些 LINE 通常位于 X 染色体上易逃脱的区域内,但靠近受 XCI 影响的基因,并与推定的内源性 siRNA 相关。因此,LINE 可能在不同层面上促进 XCI,沉默的 LINE 参与由 Xist 诱导的异染色质核区的组装,而活跃的 LINE 参与 XCI 向其他易逃脱区域的局部传播。

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