Figure 7. Activators and repressors of the 44 enriched miRNAs.

When screening the negatively correlated target genes of the 44 enriched miRNAs, we found three TFs able to up- or downregulate miRNA expression (EP300, RFX5 and FOSL2). The promoter regions of the expressed miRNAs are very similar to those of protein-coding genes. The presence of CpG islands, TATA box sequences, initiation elements and certain histone modifications indicate that the promoters of miRNA genes might be controlled by TFs. (A) RFX5 and FOSL2 both might inhibit expression of miR-192-5p, miR-93-5p and miR-138-5p in blood, although EP300 might stimulate expression of miRNAs such as miR-125-5p and miR-223-3p. (B) Unilateral or reciprocal-negative feedback loops result in oscillatory or stable mutually exclusive expressions of the TFs and miRNA components²³. For instance, EP300 might repress miR-92a expression. miR-92a targets the EP300 TF and might block its expression. Figure adapted from Krol et al.²³.