CircuitsDB: a database of mixed microRNA/transcription factor feed-forward regulatory circuits in human and mouse

Abstract

BackgroundTranscription Factors (TFs) and microRNAs (miRNAs) are key players for gene expression regulation in higher eukaryotes. In the last years, a large amount of bioinformatic studies were devoted to the elucidation of transcriptional and post-transcriptional (mostly miRNA-mediated) regulatory interactions, but little is known about the interplay between them.DescriptionHere we describe a dynamic web-accessible database, , supporting a genome-wide transcriptional and post-transcriptional regulatory network integration, for the human and mouse genomes, based on a bioinformatic sequence-analysis approach. In particular, is currently focused on the study of mixed miRNA/TF Feed-Forward regulatory Loops (FFLs), i.e. elementary circuits in which a master TF regulates an miRNA and together with it a set of Joint Target protein-coding genes. The database was constructed using an ab-initio oligo analysis procedure for the identification of the transcriptional and post-transcriptional interactions. Several external sources of information were then pooled together to obtain the functional annotation of the proposed interactions. Results for human and mouse genomes are presented in an integrated web tool, that allows users to explore the circuits, investigate their sequence and functional properties and thus suggest possible biological experiments.ConclusionsWe present , a web-server devoted to the study of human and mouse mixed miRNA/TF Feed-Forward regulatory circuits, freely available at: http://biocluster.di.unito.it/circuits/

Identification of microRNA-regulated gene networks by expression analysis of target genes

“…Previous computational methods for the identification of miRNA targets have solely relied on sequence analysis of miRNA-mRNA target sites (Bartel 2009). More recently, a number of tools introduced the use of highthroughput expression analysis to improve predictions of miRNA targets (Huang et al 2007;Ulitsky et al 2010) and the identification of gene networks controlled by miRNAs (Friard et al 2011;Huang et al 2011;Jayaswal et al 2011;Le Bechec et al 2011;Liu et al 2011;Xu et al 2011). All of the above procedures are based on the comparison of paired data sets of miRNA and mRNA expression data generated from specific microarray platforms.…”

Small Genetic Circuits and MicroRNAs: Big Players in Polymerase II Transcriptional Control in Plants

“…Circuits involving miRNAs are unique in that they can elicit particular dynamics that may be difficult to achieve by substituting a transcriptional repressor (Osella et al, 2011); interestingly, miRNAs preferentially target TFs in plants (JonesRhoades et al, 2006), creating a variety of these TF-miRNA subcircuits. One of the most well-studied examples among such cases is the miRNA-mediated feed-forward loop (Tsang et al, 2007;Friard et al, 2010) (shown in Figure 5), which is capable of eliciting a controlled genetic pulse. In general, one framework for understanding a large complex genetic network composed of multiple types of genetic interactions is to view it as a composition of smaller subcircuits, each with an identifiable function.…”

A biocomputational platform for the automated construction of large-scale mathematical models of miRNA-transcription factor networks for studies on gene dosage compensation

“…MicroRNA related data was downloaded from Mirtarbase [19] and MiRBase [20]. For gene regulation data we relied on several sources: Transmir [21], Pazar [22], TRED (Transcriptional Regulatory Element Database) [23], CircuitsDB [24].…”