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Nucleic Acids Research 2006 34(7):1947-1958; doi:10.1093/nar/gkl138
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Published online 13 April 2006

© The Author 2006. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Article

Predicting cis-acting elements of Lactobacillus plantarum by comparative genomics with different taxonomic subgroups

Michiel Wels1,2,3,*, Christof Francke1,2, Robert Kerkhoven2, Michiel Kleerebezem1,3 and Roland J. Siezen1,2,3

1 Wageningen Centre for Food Sciences PO Box 557, 6700 AN Wageningen, The Netherlands 2 Radboud University, Centre for Molecular and Biomolecular Informatics PO Box 9010, 6500 GL Nijmegen, The Netherlands 3 NIZO food research PO Box 20, 6710 BA Ede, The Netherlands

*To whom correspondence should be addressed at CMBI, Radboud University, PO Box 9010 6500 GL Nijmegen, The Netherlands. Tel: +31 024 3653398; Fax: +31 024 3652977; Email: M.Wels{at}cmbi.ru.nl

Received February 10, 2006. Revised March 1, 2006. Accepted March 15, 2006.

Cis-acting elements in Lactobacillus plantarum were predicted by comparative analysis of the upstream regions of conserved genes and predicted transcriptional units (TUs) in different bacterial genomes. TUs were predicted for two species sets, with different evolutionary distances to L.plantarum. TUs were designated ‘cluster of orthologous transcriptional units’ (COT) when >50% of the genes were orthologous in different species. Conserved DNA sequences were detected in the upstream regions of different COTs. Subsequently, conserved motifs were used to scan upstream regions of all TUs. This method revealed 18 regulatory motifs only present in lactic acid bacteria (LAB). The 18 LAB-specific candidate regulatory motifs included 13 that were not described previously. These LAB-specific different motifs were found in front of genes encoding functions varying from cold shock proteins to RNA and DNA polymerases, and many unknown functions. The best-described LAB-specific motif found was the CopR-binding site, regulating expression of copper transport ATPases. Finally, all detected motifs were used to predict co-regulated TUs (regulons) for L.plantarum, and transcriptome profiling data were analyzed to provide regulon prediction validation. It is demonstrated that phylogenetic footprinting using different species sets can identify and distinguish between general regulatory motifs and LAB-specific regulatory motifs.


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