linc-HOXA1 is a noncoding RNA that represses Hoxa1 transcription in cis
linc-HOXA1 is a noncoding RNA that represses Hoxa1 transcription in cis
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DOI：
10.1101/gad.217018.113
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发表时间：
2013-06-01
影响因子：
10.5
通讯作者：
Raj, Arjun
中科院分区：
文献类型：
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作者：
Maamar, Hedia;Cabili, Moran N.;Raj, Arjun
最近，研究人员发现胚胎干细胞中存在许多长链非编码rna (lncrna)，并认为它们是分化过程的重要调节因子。然而，只有少数例子明确地将lncRNA活性与转录调控联系起来。在这里，我们使用转录本计数和空间定位来表征小鼠胚胎干细胞中位于Hoxa基因簇50 kb处的lncRNA（称为linc-HOXA1）。单细胞转录计数显示，linc-HOXA1和Hoxa1 RNA在单细胞水平上是高度可变的，当linc-HOXA1 RNA丰度高时，Hoxa1 mRNA丰度低，反之亦然。敲低分析显示，linc-HOXA1 RNA转录位点的缺失增加了Hoxa1基因顺式到染色体的转录，而细胞暴露于维甲酸会破坏这种相互作用。我们进一步发现linc-HOXA1 RNA通过募集蛋白PURB作为转录辅助因子来抑制Hoxa1。我们的研究结果强调了转录可视化表征lncRNA功能的能力，也表明PURB可以促进lncRNA介导的转录调控。
Recently, researchers have uncovered the presence of many long noncoding RNAs (lncRNAs) in embryonic stem cells and believe they are important regulators of the differentiation process. However, there are only a few examples explicitly linking lncRNA activity to transcriptional regulation. Here, we used transcript counting and spatial localization to characterize a lncRNA (dubbed linc-HOXA1) located similar to 50 kb from the Hoxa gene cluster in mouse embryonic stem cells. Single-cell transcript counting revealed that linc-HOXA1 and Hoxa1 RNA are highly variable at the single-cell level and that whenever linc-HOXA1 RNA abundance was high, Hoxa1 mRNA abundance was low and vice versa. Knockdown analysis revealed that depletion of linc-HOXA1 RNA at its site of transcription increased transcription of the Hoxa1 gene cis to the chromosome and that exposure of cells to retinoic acid can disrupt this interaction. We further showed that linc-HOXA1 RNA represses Hoxa1 by recruiting the protein PURB as a transcriptional cofactor. Our results highlight the power of transcript visualization to characterize lncRNA function and also suggest that PURB can facilitate lncRNA-mediated transcriptional regulation.