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首页> 外文期刊>Cell Reports >Targeted Disruption of Hotair Leads to Homeotic Transformation and Gene Derepression
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Targeted Disruption of Hotair Leads to Homeotic Transformation and Gene Derepression

机译：有针对性的热风破坏导致同源转化和基因抑制。

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Long noncoding RNAs (lncRNAs) are thought to be prevalent regulators of gene expression, but the consequences of lncRNA inactivation in vivo are mostly unknown. Here, we show that targeted deletion of mouse Hotair lncRNA leads to derepression of hundreds of genes, resulting in homeotic transformation of the spine and malformation of metacarpal-carpal bones. RNA sequencing and conditional inactivation reveal an ongoing requirement of Hotair to repress HoxD genes and several imprinted loci such as Dlk1-Meg3 and Igf2-H19 without affecting imprinting choice. Hotair binds to both Polycomb repressive complex 2, which methylates histone H3 at lysine 27 (H3K27), and Lsd1 complex, which demethylates histone H3 at lysine 4 (H3K4) in vivo. Hotair inactivation causes H3K4me3 gain and, to a lesser extent, H3K27me3 loss at target genes. These results reveal the function and mechanisms of Hotair lncRNA in enforcing a silent chromatin state at Hox and additional genes.
机译：长的非编码RNA（lncRNA）被认为是基因表达的普遍调节因子，但是lncRNA在体内失活的后果却大多未知。在这里，我们显示了小鼠Hotair lncRNA的靶向缺失导致数百种基因的阻遏，导致脊柱的顺势转化和掌指骨畸形。 RNA测序和条件失活表明，Hotair一直需要抑制HoxD基因和一些印迹位点，例如Dlk1-Meg3和Igf2-H19，而不会影响印迹选择。 Hotair与在体内将赖氨酸27（H3K27）处的组蛋白H3甲基化的Polycomb抑制复合物2和在赖氨酸4（H3K4）处的组蛋白H3甲基化的Lsd1复合物结合。 Hotair失活会导致H3K4me3的获得，并在较小程度上导致目标基因的H3K27me3的丧失。这些结果揭示了Hotair lncRNA在Hox和其他基因上维持沉默染色质状态的功能和机制。

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