Combinatorial regulation of transcription factors and microRNAs.

BACKGROUND

Gene regulation is a key factor in gaining a full understanding of molecular biology. Cis-regulatory modules (CRMs), consisting of multiple transcription factor binding sites, have been confirmed as the main regulators in gene expression. In recent years, a novel regulator known as microRNA (miRNA) has been found to play an important role in gene regulation. Meanwhile, transcription factor and microRNA co-regulation has been widely identified. Thus, the relationships between CRMs and microRNAs have generated interest among biologists.

RESULTS

We constructed new combinatorial regulatory modules based on CRMs and miRNAs. By analyzing their effect on gene expression profiles, we found that genes targeted by both CRMs and miRNAs express in a significantly similar way. Furthermore, we constructed a regulatory network composed of CRMs, miRNAs, and their target genes. Investigating its structure, we found that the feed forward loop is a significant network motif, which plays an important role in gene regulation. In addition, we further analyzed the effect of miRNAs in embryonic cells, and we found that mir-154, as well as some other miRNAs, have significant co-regulation effect with CRMs in embryonic development.

CONCLUSIONS

Based on the co-regulation of CRMs and miRNAs, we constructed a novel combinatorial regulatory network which was found to play an important role in gene regulation, particularly during embryonic development.