Discovery of Conserved Motifs in Promoters of Orthologous Genes in Prokaryotes

  • Rekin’s Janky
  • Jacques van Helden
Part of the Methods in Molecular Biology™ book series (MIMB, volume 395)


We present a method to predict cis-acting elements for a given gene by detecting over-represented motifs in promoters of a set of ortholo gous genes in prokaryotes (single-gene, multiple-genomes approach). The method has been used successfully to detect regulatory elements at various taxonomical levels in prokaryotes. A web interface is available at the Regulatory Sequence Analysis Tools site (

Key Words

Transcriptional regulation pattern discovery pattern matching phylogenetic footprinting prokaryotes RSAT get-orthologs retrieve-seq dyad-analysis 



This work was supported by a doctoral grant from Fonds pour la Recherche dans l'Industrie et l'Agriculture (F.R.I.A.) to RJ and by the “BioSapiens Network of Excellence” funded under the sixth Framework programme of the European Communities (LSHG-CT-2003-503265). Genome installation and orthologs identification are done on a 40-node PC cluster contributed by various institutions, including the Belgian Fonds pour la Recherche Fondamentale Collective (F.R.F.C. grant 2005). We are grateful to Raphaël Leplae for his enthusiasm in obtaining, installing, and maintaining this cluster. JvH acknowledges Stéphane Vissers for an inspiring discussion on the importance of good quality protocols for teaching and practicing good science. We are thankful to Stephan Kurtz for making available his very efficient program vmatch, which we use to purge redundant fragments.


  1. 1.
    Tagle, D. A., Koop, B. F., Goodman, M., Slightom, J. L., Hess, D. L., and Jones, R. T. (1988) Embryonic epsilon and gamma globin genes of a prosimian primate (Galago crassicaudatus). Nucleotide and amino acid sequences, developmental regulation and phylogenetic footprints. J. Mol. Biol. 203, 439–455.CrossRefPubMedGoogle Scholar
  2. 2.
    Wasserman, W. W. and Fickett, J. W. (1998) Identification of regulatory regions which confer muscle-specific gene expression. J. Mol. Biol. 278, 167–181.CrossRefPubMedGoogle Scholar
  3. 3.
    Fickett, J. W., and Wasserman, W. W. (2000) Discovery and modeling of transcriptional regulatory regions. Curr. Opin. Biotechnol. 11, 19–24.CrossRefPubMedGoogle Scholar
  4. 4.
    Tompa, M. (2001) Identifying functional elements by comparative DNA sequence analysis. Genome Res. 11, 1143–1144.CrossRefPubMedGoogle Scholar
  5. 5.
    McGuire, A. M., Hughes, J. D., and Church, G. M. (2000) Conservation of DNA regulatory motifs and discovery of new motifs in microbial genomes. Genome Res. 10, 744–757.CrossRefPubMedGoogle Scholar
  6. 6.
    McCue, L., Thompson, W., Carmack, C., et al. (2001) Phylogenetic footprinting of transcription factor binding sites in proteobacterial genomes. Nucleic Acids Res. 29, 774–782.CrossRefPubMedGoogle Scholar
  7. 7.
    Alkema, W. B., Lenhard, B., and Wasserman, W. W. (2004) Regulog analysis: detection of conserved regulatory networks across bacteria: application to Staphylococcus aureus. Genome Res. 14, 1362–1373.CrossRefPubMedGoogle Scholar
  8. 8.
    van Helden, J., Andre, B., and Collado-Vides, J. (1998) Extracting regulatory sites from the upstream region of yeast genes by computational analysis of oligonucleotide frequencies. J. Mol. Biol. 281, 827–842.CrossRefPubMedGoogle Scholar
  9. 9.
    Hertz, G. Z., Hartzell, G. W., III, and Stormo, G. D. (1990) Identification of consensus patterns in unaligned DNA sequences known to be functionally related. Comput. Appl. Biosci. 6, 81–92.PubMedGoogle Scholar
  10. 10.
    Hertz, G. Z. and Stormo, G. D. (1999) Identifying DNA and protein patterns with statistically significant alignments of multiple sequences. Bioinformatics 15, 563–577.CrossRefPubMedGoogle Scholar
  11. 11.
    Lawrence, C. E., Altschul, S. F., Boguski, M. S., Liu, J. S., Neuwald, A. F., and Wootton, J. C. (1993) Detecting subtle sequence signals: a Gibbs sampling strategy for multiple alignment. Science 262, 208–214.CrossRefPubMedGoogle Scholar
  12. 12.
    Neuwald, A. F., Liu, J. S., and Lawrence, C. E. (1995) Gibbs motif sampling: detection of bacterial outer membrane protein repeats. Protein Sci. 4, 1618–1632.CrossRefPubMedGoogle Scholar
  13. 13.
    Andrews, A. E., Dickson, B., Lawley, B., Cobbett, C., and Pittard, A. J. (1991) mportance of the position of TYR R boxes for repression and activation of the tyrP and aroF genes in Escherichia coli. J. Bacteriol. 173, 5079–5085.PubMedGoogle Scholar
  14. 14.
    Pittard, A. J. and Davidson, B. E. (1991) TyrR protein of Escherichia coli and its role as repressor and activator. Mol. Microbiol. 5, 1585–1592.CrossRefPubMedGoogle Scholar
  15. 15.
    Yang, J., Wang, P., and Pittard, A. J. (1999) Mechanism of repression of the aroP P2 promoter by the TyrR protein of Escherichia coli. J. Bacteriol. 181, 6411–6418.PubMedGoogle Scholar
  16. 16.
    Whipp, M. J. and Pittard, A. J. (1977) Regulation of aromatic amino acid transport systems in Escherichia coli K-12. J. Bacteriol. 132, 453–461.PubMedGoogle Scholar
  17. 17.
    Altschul, S. F., Gish, W., Miller, W., Myers, E. W., and Lipman, D. J. (1990) Basic local alignment search tool. J. Mol. Biol. 215, 403–410.PubMedGoogle Scholar
  18. 18.
    Altschul, S. F., Madden, T. L., Schaffer, A. A., et al. (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25, 3389–3402.CrossRefPubMedGoogle Scholar
  19. 19.
    Perez-Rueda, E., and Collado-Vides, J. (2000) The repertoire of DNA-binding transcriptional regulators in Escherichia coli K-12. Nucleic Acids Res. 28, 1838–1847.CrossRefPubMedGoogle Scholar
  20. 20.
    van Helden, J., del Olmo, M., and Perez-Ortin, J. E. (2000) Statistical analysis of yeast genomic downstream sequences reveals putative polyadenylation signals. Nucleic Acids Res. 28, 1000–1010.CrossRefPubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • Rekin’s Janky
    • 1
  • Jacques van Helden
    • 2
  1. 1.Universite Libre de BruxellesBrusselsBelgium
  2. 2.Service de Conformation des Macromolécules Biologiques et de Bioinformatique (SCMBB)Université Libre de BruxellesBrusselsBelgium

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