The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome.

The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome.
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DOI:
10.1126/science.1237973
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发表时间:
2013-08-16
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Guttman M
Guttman M
中科院分区:
其他
文献类型:
--
作者:
Engreitz JM;Pandya-Jones A;McDonel P;Shishkin A;Sirokman K;Surka C;Kadri S;Xing J;Goren A;Lander ES;Plath K;Guttman M

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许多大的非编码RNA(LncRNAs)调节染色质,但它们定位于基因组靶标的机制仍未被探索。在这里,我们研究了Xist lncRNA在X染色体失活(XCI)过程中的定位机制,XCI是一种由lncRNA介导的染色质调节范例。在XCI的维持过程中,Xist广泛地结合在X染色体上。在XCI的启动过程中,Xist最初转移到X染色体上不是由特定序列定义的远端区域。相反,Xist通过利用X染色体的三维构象来识别这些区域。XIST需要它的沉默结构域扩散到活跃转录的区域,从而访问整个染色体。这提出了一种模型,在该模型中,Xist通过在三维中搜索、修改染色体结构并传播到新的可访问位置来覆盖X染色体。
Many large noncoding RNAs (lncRNAs) regulate chromatin, but the mechanisms by which they localize to genomic targets remain unexplored. Here we investigate the localization mechanisms of the Xist lncRNA during X-chromosome inactivation (XCI), a paradigm of lncRNA-mediated chromatin regulation. During the maintenance of XCI, Xist binds broadly across the X-chromosome. During initiation of XCI, Xist initially transfers to distal regions across the X-chromosome that are not defined by specific sequences. Instead, Xist identifies these regions by exploiting the three-dimensional conformation of the X-chromosome. Xist requires its silencing domain to spread across actively transcribed regions and thereby access the entire chromosome. This suggests a model where Xist coats the X-chromosome by searching in three dimensions, modifying chromosome structure, and spreading to newly accessible locations.
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