UMMS Affiliation
Graduate School of Biomedical Sciences; Program in Gene Function and Expression; Program in Molecular Medicine
Date
9-17-2008
Document Type
Article
Medical Subject Headings
Animals; Animals, Genetically Modified; Caenorhabditis elegans; *Genome; MicroRNAs; Polymerase Chain Reaction; Transcription, Genetic
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
MicroRNAs (miRNAs) and transcription factors (TFs) are primary metazoan gene regulators. Whereas much attention has focused on finding the targets of both miRNAs and TFs, the transcriptional networks that regulate miRNA expression remain largely unexplored. Here, we present the first genome-scale Caenorhabditis elegans miRNA regulatory network that contains experimentally mapped transcriptional TF --> miRNA interactions, as well as computationally predicted post-transcriptional miRNA --> TF interactions. We find that this integrated miRNA network contains 23 miRNA <--> TF composite feedback loops in which a TF that controls a miRNA is itself regulated by that same miRNA. By rigorous network randomizations, we show that such loops occur more frequently than expected by chance and, hence, constitute a genuine network motif. Interestingly, miRNAs and TFs in such loops are heavily regulated and regulate many targets. This "high flux capacity" suggests that loops provide a mechanism of high information flow for the coordinate and adaptable control of miRNA and TF target regulons.
Y1H dataset can be found as a supplemental file to this paper. See Additional Files below.
Rights and Permissions
Citation: Genes Dev. 2008 Sep 15;22(18):2535-49. Link to article on publisher's site
Related Resources
Y1H dataset (XLS, 100 KB)