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Open Access Highly Accessed Research article

Combinatorial regulation of transcription factors and microRNAs

Naifang Su1, Yufu Wang1, Minping Qian12 and Minghua Deng123*

Author Affiliations

1 LMAM, School of Mathematical Sciences, Peking University, Beijing 100871, China

2 Center for Theoretical Biology, Peking University, Beijing 100871, China

3 Center for Statistical Science, Peking University, Beijing 100871, China

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BMC Systems Biology 2010, 4:150  doi:10.1186/1752-0509-4-150

Published: 8 November 2010



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.


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.


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.