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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
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.
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.
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.
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.
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.
Lenhard, B. and Wasserman, W. W. (2002) TFBS: computational framework for transcription factor binding site analysis. Bioinformatics 18, 1135–1136.
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.
Cartharius, K., Frech, K., Grote, K., et al. (2005) MatInspector and beyond: promoter analysis based on transcription factor binding sites. Bioinformatics 21, 2933–2942.
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.
Stormo, G. D. (2000) DNA binding sites: representation and discovery. Bioinformatics 16, 16–23.
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.
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.
Tompa, M. (2001) Identifying functional elements by comparative DNA sequence analysis. Genome Res. 11, 1143–1144.
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.
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.
Bray, N., Dubchak, I., and Pachter, L. (2003) AVID: a global alignment program. Genome Res. 13, 97–102.
Schwartz, S., Kent, W. J., Smit, A., et al. (2003) Human-mouse alignments with BLASTZ. Genome Res. 13, 103–107.
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.
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.
Birney, E., Andrews, D., Caccamo, M., et al. (2006) Ensembl 2006. Nucleic Acids Res. 34, D556–D561.
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.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2007 Humana Press Inc.
About this protocol
Cite this protocol
Berezikov, E., Guryev, V., Cuppen, E. (2007). Exploring Conservation of Transcription Factor Binding Sites with CONREAL. In: Bergman, N.H. (eds) Comparative Genomics. Methods in Molecular Biology™, vol 395. Humana Press. https://doi.org/10.1007/978-1-59745-514-5_27
Download citation
DOI: https://doi.org/10.1007/978-1-59745-514-5_27
Publisher Name: Humana Press
Print ISBN: 978-1-58829-693-1
Online ISBN: 978-1-59745-514-5
eBook Packages: Springer Protocols