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Please use this identifier to cite or link to this item: http://hdl.handle.net/10481/28447

Title: Identifying promoter features of co-regulated genes with similar network motifs
Authors: Harari, Oscar
Val, Coral del
Romero-Zaliz, Rocío
Shin, Dongwoo
Huang, Henry
Groisman, Eduardo A.
Zwir, Igor
Issue Date: 2009
Abstract: Background: A large amount of computational and experimental work has been devoted to uncovering network motifs in gene regulatory networks. The leading hypothesis is that evolutionary processes independently selected recurrent architectural relationships among regulators and target genes (motifs) to produce characteristic expression patterns of its members. However, even with the same architecture, the genes may still be differentially expressed. Therefore, to define fully the expression of a group of genes, the strength of the connections in a network motif must be specified, and the cis-promoter features that participate in the regulation must be determined.
Results: We have developed a model-based approach to analyze proteobacterial genomes for promoter features that is specifically designed to account for the variability in sequence, location and topology intrinsic to differential gene expression. We provide methods for annotating regulatory regions by detecting their subjacent cis-features. This includes identifying binding sites for a transcriptional regulator, distinguishing between activation and repression sites, direct and reverse orientation, and among sequences that weakly reflect a particular pattern; binding sites for the RNA polymerase, characterizing different classes, and locations relative to the transcription factor binding sites; the presence of riboswitches in the 5'UTR, and for other transcription factors. We applied our approach to characterize network motifs controlled by the PhoP/PhoQ regulatory system of Escherichia coli and Salmonella enterica serovar Typhimurium. We identified key features that enable the PhoP protein to control its target genes, and distinct features may produce different expression patterns even within the same network motif.
Conclusion: Global transcriptional regulators control multiple promoters by a variety of network motifs. This is clearly the case for the regulatory protein PhoP. In this work, we studied this regulatory protein and demonstrated that understanding gene expression does not only require identifying a set of connexions or network motif, but also the cis-acting elements participating in each of these connexions.
Sponsorship: This research was supported in part by the Spanish Ministry of Science and Technology under project TIN2006-12879 and by Consejería de Innovacion, Investigación y Ciencia de la de la Junta de Andalucía under project TIC02788.
Publisher: Biomed Central
Description: Proceedings of the IEEE International Conference on Bioinformatics and Biomedicine (BIBM) 2008, Philadelphia, PA, USA. 3–5 November 2008.
Keywords: Computational biology
DNA-Directed RNA Polymerases
Escherichia-coli
Regulatory networks
Salmonella typhi
Transcription factors
URI: http://hdl.handle.net/10481/28447
ISSN: 1471-2105
Citation: Harari, O.; et al. Identifying promoter features of co-regulated genes with similar network motifs. BMC Bioinformatics 10(sup4): S1 (2009). [http://hdl.handle.net/10481/28447]
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