Genome-wide analysis of enhancer RNA in gene regulation across 12 mouse tissues.
Genome-wide analysis of enhancer RNA in gene regulation across 12 mouse tissues.
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在12个小鼠组织中基因调节中增强子RNA的全基因组分析。
DOI：
10.1038/srep12648
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发表时间：
2015-07-29
影响因子：
4.6
通讯作者：
Tsai HK
中科院分区：
文献类型：
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作者：
Cheng JH;Pan DZ;Tsai ZT;Tsai HK
增强子在基因调控中起着至关重要的作用，但增强子转录产物(即增强子RNA，eRNAs)在调控系统中的作用尚不清楚。我们使用12个小鼠组织的全基因组数据对eRNA进行了计算分析。转录增强子靶向基因的表达与Erna的表达呈正相关，且显著高于非转录增强子靶向基因的表达。这一结果表明Erna转录指示了一种增强子状态，进一步增加了基因的表达。这种增强子的状态是组织特有的，因为相同的增强子在组织中差异转录eRNA。因此，eRNAs的存在描述了一种组织特异性的增强子状态，通常与较高表达的靶基因相关，推测eRNAs是否具有基因激活潜力。我们进一步发现，大量的eRNAs含有序列和二级结构与microRNAs相似的区域。有趣的是，最近越来越多的研究假设，当靶向启动子序列时，microRNAs可能从一般的抑制作用转换为激活作用。总之，我们的结果提供了推测，eRNAs可能与增强子目标基因的选择性激活有关。
Enhancers play a crucial role in gene regulation but the participation of enhancer transcripts (i.e. enhancer RNA, eRNAs) in regulatory systems remains unclear. We provide a computational analysis on eRNAs using genome-wide data across 12 mouse tissues. The expression of genes targeted by transcribing enhancer is positively correlated with eRNA expression and significantly higher than expression of genes targeted by non-transcribing enhancers. This result implies eRNA transcription indicates a state of enhancer that further increases gene expression. This state of enhancer is tissue-specific, as the same enhancer differentially transcribes eRNAs across tissues. Therefore, the presence of eRNAs describes a tissue-specific state of enhancer that is generally associated with higher expressed target genes, surmising as to whether eRNAs have gene activation potential. We further found a large number of eRNAs contain regions in which sequences and secondary structures are similar to microRNAs. Interestingly, an increasing number of recent studies hypothesize that microRNAs may switch from their general repressive role to an activating role when targeting promoter sequences. Collectively, our results provide speculation that eRNAs may be associated with the selective activation of enhancer target genes.