Bioinformatics Advance Access published online on November 24, 2007
Bioinformatics, doi:10.1093/bioinformatics/btm572
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Identification of phylogenetically conserved microRNA cis-regulatory elements across 12 Drosophila
1MOE Key Laboratory of Bioinformatics and Bioinformatics Div, TNLIST / Department of Automation, Tsinghua University, Beijing 100084, China and
2Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11274, USA
*To whom correspondence should be addressed. Xiaowo Wang, E-mail: daulyd{at}tsinghua.edu.cn
| Abstract |
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Motivation: MicroRNAs are a class of endogenous small RNAs that play regulatory roles. Intergenic miRNAs are believed to be transcribed independently, but the transcriptional control of these crucial regulators is still poorly understood.
Results: In this work, phylogenetic footprinting is used to identify conserved cis-regulatory elements (CCEs) surrounding intergenic miRNAs in Drosophila. With a two-step strategy that takes the advantage of both alignment-based and motif-based methods, we identified cis-regulatory elements that are conserved across the twelve fly species. When compared with TRANSFAC database, these CCEs are significantly enriched in known transcription factor binding sites (TFBSs). Moreover, several TFs that play essential role in Drosophila development (e.g. Adf-1, Abd-B, Sd, Prd, Ubx, Zen and En) are found to be preferentially regulating the miRNA genes. Further analysis revealed many over-represented cis-regulatory modules (CRMs) composed of multiple known TFBSs, motif pairs with significant distance constraints and a number of de novo motifs, many of which preferentially occur near the transcription start site of protein-coding genes. Additionally, a number of putative miRNA-TF regulatory feedback loops were also detected.
Availability: Supplementary information and the Perl scripts performing two-step phylogenetic footprinting are available at http://bioinfo.au.tsinghua.edu.cn/member/xwwang/mircisreg
Contact: daulyd{at}tsinghua.edu.cn
Associate Editor: Dr. Limsoon Wong
Received on May 14, 2007; revised on July 18, 2007; accepted on November 9, 2007
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