Advertisement

Exploring Conservation of Transcription Factor Binding Sites with CONREAL

  • Eugene Berezikov
  • Victor Guryev
  • Edwin Cuppen
Part of the Methods in Molecular Biology™ book series (MIMB, volume 395)

Summary

Prediction of transcription factor binding sites (TFBS) is commonly used to formulate working hypotheses for experimental studies on gene regulation. Computational identification of functional TFBS is complicated because of short length and degeneracy of sequence motifs recognized by transcription factors. Information on conservation of predicted sites in orthologous sequences from different species (phylogenetic footprinting) can be used to distinguish potentially functional elements from background predictions. Results of phylogenetic footprinting may substantially depend on the algorithm used to construct an alignment of orthologous sequences, from which conservation of predicted TFBS is estimated. The CONREAL web server allows prediction and comparison of conserved TFBS based on AVID, BLASTZ, CONREAL, and LAGAN alignments. The web tool is particularly suited for the analysis of individual genes or genomic regions, although the underlying algorithm can also be used in high-throughput promoter analysis.

Key Words

Transcription factor binding site regulatory element promoter phylogenetic footprinting orthologous sequence alignment 

References

  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.
    Gumucio, D. L., Heilstedt-Williamson, H., Gray, T. A., et al. (1992) Phylogenetic footprinting reveals a nuclear protein which binds to silencer sequences in the human gamma and epsilon globin genes. Mol. Cell. Biol. 12, 4919–4929.PubMedGoogle Scholar
  3. 3.
    Aparicio, S., Morrison, A., Gould, A., et al. (1995) Detecting conserved regulatory elements with the model genome of the Japanese puffer fish, Fugu rubripes. Proc. Natl. Acad. Sci. USA 92, 1684–1688.CrossRefPubMedGoogle Scholar
  4. 4.
    Loots, G. G., Locksley, R. M., Blankespoor, C. M., et al. (2000) Identification of a coordinate regulator of interleukins 4, 13, and 5 by cross-species sequence comparisons. Science 288, 136–140.CrossRefPubMedGoogle Scholar
  5. 5.
    Wasserman, W. W., Palumbo, M., Thompson, W., Fickett, J. W., and Lawrence, C. E. (2000) Human-mouse genome comparisons to locate regulatory sites. Nat. Genet. 26, 225–228.CrossRefPubMedGoogle Scholar
  6. 6.
    Lenhard, B. and Wasserman, W. W. (2002) TFBS: computational framework for transcription factor binding site analysis. Bioinformatics 18, 1135–1136.CrossRefPubMedGoogle Scholar
  7. 7.
    Kel, A. E., Gossling, E., Reuter, I., Cheremushkin, E., Kel-Margoulis, O. V., and Wingender, E. (2003) MATCH: a tool for searching transcription factor binding sites in DNA sequences. Nucleic Acids Res. 31, 3576–3579.CrossRefPubMedGoogle Scholar
  8. 8.
    Cartharius, K., Frech, K., Grote, K., et al. (2005) MatInspector and beyond: promoter analysis based on transcription factor binding sites. Bioinformatics 21, 2933–2942.CrossRefPubMedGoogle Scholar
  9. 9.
    Matys, V., Kel-Margoulis, O. V., Fricke, E., et al. (2006) TRANSFAC and its module TRANSCompel: transcriptional gene regulation in eukaryotes. Nucleic Acids Res. 34, D108–D110.CrossRefPubMedGoogle Scholar
  10. 10.
    Stormo, G. D. (2000) DNA binding sites: representation and discovery. Bioinformatics 16, 16–23.CrossRefPubMedGoogle Scholar
  11. 11.
    Vlieghe, D., Sandelin, A., De Bleser, P. J., et al. (2006) A new generation of JASPAR, the open-access repository for transcription factor binding site profiles. Nucleic Acids Res. 34, D95–D97.CrossRefPubMedGoogle Scholar
  12. 12.
    Cliften, P. F., Hillier, L. W., Fulton, L., et al. (2001) Surveying Saccharomyces genomes to identify functional elements by comparative DNA sequence analysis. Genome Res. 11, 1175–1186.CrossRefPubMedGoogle Scholar
  13. 13.
    Tompa, M. (2001) Identifying functional elements by comparative DNA sequence analysis. Genome Res. 11, 1143–1144.CrossRefPubMedGoogle Scholar
  14. 14.
    Thompson, J. D., Higgins, D. G., and Gibson, T. J. (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 22, 4673–4680.CrossRefPubMedGoogle Scholar
  15. 15.
    Brudno, M., Do, C. B., Cooper, G. M., et al. (2003) LAGAN and Multi-LAGAN: efficient tools for large-scale multiple alignment of genomic DNA. Genome Res. 13, 721–731.CrossRefPubMedGoogle Scholar
  16. 16.
    Bray, N., Dubchak, I., and Pachter, L. (2003) AVID: a global alignment program. Genome Res. 13, 97–102.CrossRefPubMedGoogle Scholar
  17. 17.
    Schwartz, S., Kent, W. J., Smit, A., et al. (2003) Human-mouse alignments with BLASTZ. Genome Res. 13, 103–107.CrossRefPubMedGoogle Scholar
  18. 18.
    Berezikov, E., Guryev, V., Plasterk, R. H., and Cuppen, E. (2004) CONREAL: conserved regulatory elements anchored alignment algorithm for identification of transcription factor binding sites by phylogenetic footprinting. Genome Res. 14, 170–178.CrossRefPubMedGoogle Scholar
  19. 19.
    Berezikov, E., Guryev, V., and Cuppen, E. (2005) CONREAL web server: identification and visualization of conserved transcription factor binding sites. Nucleic Acids Res. 33, W447–W450.CrossRefPubMedGoogle Scholar
  20. 20.
    Birney, E., Andrews, D., Caccamo, M., et al. (2006) Ensembl 2006. Nucleic Acids Res. 34, D556–D561.CrossRefPubMedGoogle Scholar
  21. 21.
    Nishizaki, Y., Shimazu, K., Kondoh, H., and Sasaki, H. (2001) Identification of essential sequence motifs in the node/notochord enhancer of Foxa2 (Hnf3beta) gene that are conserved across vertebrate species. Mech. Dev. 102, 57–66.CrossRefPubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • Eugene Berezikov
    • 1
  • Victor Guryev
    • 2
  • Edwin Cuppen
    • 3
  1. 1.Hubrecht LaboratoryUtrecht, NL
  2. 2.Hubrecht LaboratoryUtrecht, NL
  3. 3.Hubrecht LaboratoryUtrecht, NL

Personalised recommendations