Integrating epigenetic marks for identification of transcriptionally active miRNAs

MicroRNAs have been identified as important regulators involved in biological processes and human diseases. We proposed a computational approach to systematic identification of active promoters of miRNAs by active models using epigenetic characteristics at active promoters of protein-coding genes together with a genomic context-based filtering step in nine human cell types, which were validated to exhibit greater conservation, more overlap with CAGE-identified TSSs, more conserved TFBSs and higher transcription factor binding signal intensities. Furthermore, expression analysis showed discordance between transcriptional activation of miRNAs and expression of their precursor and mature forms, indicating that precursor and mature miRNA expression is insufficient to account for transcriptional activation of miRNAs. Compared to other methods, our approach identified higher percentages of active miRNAs with CAGE-detected TSS activity and primary transcript expression, further supporting the validity of our approach, which will be valuable to understand the biological roles of miRNAs in specific cell contexts.