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Bioinformatics Advance Access originally published online on November 24, 2007
Bioinformatics 2008 24(2):165-171; doi:10.1093/bioinformatics/btm572
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© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Identification of phylogenetically conserved microRNA cis-regulatory elements across 12 Drosophila species

Xiaowo Wang 1, Jin Gu 1, Michael Q. Zhang 1,2 and Yanda Li 1,*

1MOE Key Laboratory of Bioinformatics and Bioinformatics Division, TNLIST/Department of Automation, Tsinghua University, Beijing 100084, China and 2Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA

*To whom correspondence should be addressed.


  Abstract

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 advantage of both alignment-based and motif-based methods, we identified CCEs that are conserved across the 12 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 roles 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 novel 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 Material 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

Supplementary information: Supplementary data are available at Bioinformatics online.

Associate Editor: Limsoon Wong

Received on May 14, 2007; revised on July 18, 2007; accepted on November 9, 2007

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