Genome-wide analysis of enhancer RNA in gene regulation across 12 mouse tissues

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.