Production of Spliced Long Noncoding RNAs Specifies Regions with Increased Enhancer Activity
Production of Spliced Long Noncoding RNAs Specifies Regions with Increased Enhancer Activity
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DOI：
10.1016/j.cels.2018.10.009
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发表时间：
2018-11-28
期刊：
影响因子：
9.3
通讯作者：
Ulitsky, Igor
中科院分区：
文献类型：
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作者：
Gil, Noa;Ulitsky, Igor
哺乳动物中的活性增强子产生的增强子rna （erna）是双向转录的、未剪接的和不稳定的。增强子区域还富含长链非编码RNA （lncRNA）转录本，这些转录本通常是剪接的，基本上更稳定。为了探索这两类rna之间的关系，我们分析了dna酶超敏感位点，这些位点具有双向转录的证据，我们称之为dna产生中心（EPCs）。发现非常靠近lncrna转录起始位点的EPCs具有增强子和启动子的属性，包括独特的DNA基序和独特的染色质景观。这些EPCs与更高的增强子活性相关，至少部分是由促进lncRNA产生的保守的定向剪接信号驱动的，这表明lncRNA加工在增强子活性中起着因果作用。总之，我们的研究结果表明，一些增强子产生lncRNA的保守能力可能通过lncRNA成熟介导的方式增强了它们的活性。
Active enhancers in mammals produce enhancer RNAs (eRNAs) that are bidirectionally transcribed, unspliced, and unstable. Enhancer regions are also enriched with long noncoding RNA (lncRNA) transcripts, which are typically spliced and substantially more stable. In order to explore the relationship between these two classes of RNAs, we analyzed DNase hypersensitive sites with evidence of bidirectional transcription, which we termed eRNA-producing centers (EPCs). EPCs found very close to transcription start sites of lncRNAs exhibit attributes of both enhancers and promoters, including distinctive DNA motifs and a characteristic chromatin landscape. These EPCs are associated with higher enhancer activity, driven at least in part by the presence of conserved, directional splicing signals that promote lncRNA production, pointing at a causal role of lncRNA processing in enhancer activity. Together, our results suggest that the conserved ability of some enhancers to produce lncRNAs augments their activity in a manner likely mediated through lncRNA maturation.