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Long ncRNA expression associates with tissue-specific enhancers

机译：ncRNA的长表达与组织特异性增强子有关

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Long non-coding RNAs (ncRNA) have recently been demonstrated to be expressed from a subset of enhancers and to be required for the distant regulation of gene expression. Several approaches to predict enhancers have been developed based on various chromatin marks and occupancy of enhancer-binding proteins. Despite the rapid advances in the field, no consensus how to define tissue specific enhancers yet exists. Here, we identify 2,695 long ncRNAs annotated by ENCODE (corresponding to 28% of all ENCODE annotated long ncRNAs) that overlap tissue-specific enhancers. We use a recently developed algorithm to predict tissue-specific enhancers, PreSTIGE, that is based on the H3K4me1 mark and tissue specific expression of mRNAs. The expression of the long ncRNAs overlapping enhancers is significantly higher when the enhancer is predicted as active in a specific cell line, suggesting a general interdependency of active enhancers and expression of long ncRNAs. This dependency is not identified using previous enhancer prediction algorithms that do not account for expression of their downstream targets. The predicted enhancers that overlap annotated long ncRNAs generally have a lower ratio of H3K4me1 to H3K4me3, suggesting that enhancers expressing long ncRNAs might be associated with specific epigenetic marks. In conclusion, we demonstrate the tissue-specific predictive power of PreSTIGE and provide evidence for thousands of long ncRNAs that are expressed from active tissue-specific enhancers, suggesting a particularly important functional relationship between long ncRNAs and enhancer activity in determining tissue-specific gene expression.
机译：最近已证明长非编码RNA（ncRNA）从增强子的子集表达，并且是基因表达的远距离调节所必需的。基于各种染色质标记和增强子结合蛋白的占有率，已经开发了几种预测增强子的方法。尽管在该领域中有快速的进步，但是关于如何定义组织特异性增强剂尚无共识。在这里，我们确定了2695个由ENCODE注释的长ncRNA（相当于所有带ENCODE注释的长ncRNA的28％）与组织特异性增强子重叠。我们使用一种最新开发的算法来预测组织特异性增强子PreSTIGE，它基于H3K4me1标记和mRNA的组织特异性表达。当预测增强子在特定细胞系中具有活性时，长ncRNA重叠增强子的表达明显更高，这表明活性增强子与长ncRNA的表达之间普遍存在相互依赖性。使用以前的增强子预测算法无法识别此依赖性，该算法不考虑其下游目标的表达。与带注释的长ncRNA重叠的预测增强子通常具有较低的H3K4me1与H3K4me3比率，这表明表达长ncRNA的增强子可能与特定的表观遗传标记有关。总之，我们证明了PreSTIGE的组织特异性预测能力，并为数千个从活性组织特异性增强子表达的长ncRNA提供了证据，表明长ncRNA与增强子活性之间的特别重要的功能关系在确定组织特异性基因表达中。

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