Abstract
Finding the regulatory mechanisms responsible for gene expression remains one of the most important challenges for biomedical research. A major focus in cellular biology is to find functional transcription factor binding sites (TFBS) responsible for the regulation of a downstream gene. As wet-lab methods are time consuming and expensive, it is not realistic to identify TFBS for all uncharacterized genes in the genome by purely experimental means. Computational methods aimed at predicting potential regulatory regions can increase the efficiency of wet-lab experiments significantly. Here, methods for building quantitative models describing the binding preferences of transcription factors based on literature-derived data are presented, as well as a general protocol for scanning promoters using cross-species comparison as a filter (phylogenetic footprinting).
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References
Stormo, G. D. (2000) DNA binding sites: representation and discovery.Bioinformatics 16, 16–23.
Wasserman, W. W., Sandelin, A. (2004) Applied bioinformatics for the identification of regulatory elements.Nat Rev Genet 5, 276–287.
Fickett, J. W. (1996) Quantitative discrimination of MEF2 sites.Mol Cell Biol 16,437–441.
Wasserman, W. W., Fickett, J. W. (1998) Identification of regulatory regions which confer muscle-specific gene expression.J Mol Biol 278, 167–181.
Lenhard,B.,Sandelin,A.,Mendoza,L.,et al. (2003) Identification of conserved regulatory elements by comparative genome analysis.j Biol 2, 13.
Wasserman, W. W., Palumbo, M., Thompson, W., et al. (2000) Human-mouse genome comparisons to locate regulatory sites.Nat Genet 26, 225–228.
Alberts, B., Johnson, A., Lewis, J., et al. (2002)Molecular Biology of the Cell. Garland Publishing, New York.
Kadonaga, J. T. (2004) Regulation of RNA polymerase II transcription by sequence-specific DNA binding factors.Cell 116, 247–257.
Lewin, B. (2004)Genes VIII. Pearsson Education, New York.
Bailey, T. L., Elkan, C. (1995) The value of prior knowledge in discovering motifs with MEME.Proc Int Conf Intell Syst Mol Biol 3, 21–29.
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, D95–97.
Sandelin, A., Wasserman, W W., Lenhard, B. (2004) ConSite: web-based prediction of regulatory elements using cross-species comparison.Nucleic Acids Res 32, W249–252.
Lenhard, B., Wasserman, W W (2002) TFBS: Computational framework for transcription factor binding site analysis.Bioinformatics 18, 1135–1136.
Matys, V., Kel-Margoulis, O. V., Fricke, E., et al. (2006) TRANSFAC and its module TEANSCompel: transcriptional gene regulation in eukaryotes.Nucleic Acids Res 34, D108–110.
Pollock, R, Treisman, R (1990) A sensitive method for the determination of protein-DNA binding specificities.Nucleic Acids Res 18, 6197–6204.
Rice, P., Longden, I., Bleasby, A. (2000) EMBOSS: the European Molecular Biology Open Software Suite.Trends Genet 16, 276–277.
Durbin, R, Eddy, S. R., Krogh, A., et al. (2001)Biological Sequence Analysis. Cambridge Press, Cambridge, UK.
Schneider, T. D., Stephens, R M. (1990) Sequence logos: a new way to display consensus sequences.Nucleic Acids Res 18, 6097–7100.
Pierrou, S., Hellqvist, M., Samuelsson, L., et al. (1994) Cloning and characterization of seven human forkhead proteins: binding site specificity and DNA bending.Embo J 13, 5002–5012.
Workman, C. T., Stormo, G. D. (2000) ANN-Spec: a method for discovering transcription factor binding sites with improved specificity.Pac Symp Biocomput 467–478.
Hinrichs, A. S., Karolchik, D., Baertsch, R., et al. (2006) The UCSC Genome Browser Database: update 2006.Nucleic Acids Res 34, D590–598.
King, D. C, Taylor, J., Elnitski, L., et al. (2005) Evaluation of regulatory potential and conservation scores for detecting cis-regula-tory modules in aligned mammalian genome sequences.Genome Res 15, 1051–1060.
Carninci, P., Kasukawa, T, Katayama, S., et al. (2005) The transcriptional landscape of the mammalian genome.Science 309, D556–561.
Birney, E., Andrews, D., Caccamo, M.,et al. (2006) Ensembl 2006.Nucleic Acids Res 34, D556–561.
Carninci, P., Sandelin, A., Lenhard, B., et al. (2006) Genome-wide analysis of mammalian promoter architecture and evolution,Nat Genet 38, 626–635.
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.
Schwartz, S., Kent, W J., Smit, A., et al. (2003) Human-mouse alignments with BLASTZ.Genome Res 13,103–107.
Blanchette, M., Kent, W. J., Riemer, C, et al. (2004) Aligning multiple genomic sequences with the threaded blockset aligner.Genome Res 14, 708–715.
Altschul, S. F, Gish, W., Miller, W., et al. (1990) Basic local alignment search tool.J Mol Biol 215, 403–410.
Loots, G. G., Ovcharenko, I., Pachter, L., et al. (2002) rVista for comparative sequence-based discovery of functional transcription factor binding sites.Genome Res 12, 832–839.
Puig, O., Tjian, R. (2005) Transcriptional feedback control of insulin receptor by dFOXO/ FOXO1.Genes Dev 19, 2435–2446.
Koonin, E. V. (2005) Orthologs, paralogs, and evolutionary genomics.Annu Rev Genet 39, 309–338.
Dermitzakis, E. T., Clark, A. G. (2002) Evolution of transcription factor binding sites in mammalian gene regulatory regions: conservation and turnover.Mol Biol Evol 19,1114–1121.
Frith, M., Ponjavic, J., Fredman, D., et al. (2006) Evolutionary turnover of mammalian transcription start sites.Genome Res 16, 713–722.
Gomez-Skarmeta, J. L., Lenhard, B., Becker, T. S. (2006) New technologies, new findings, and new concepts in the study of vertebrate cis-regulatory sequences.Dev Dyn 235, 870–885.
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Thanks to Ann Karlsson for comments on the text.
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© 2008 Humana Press, a part of Springer Science+Business Media, LLC
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Sandelin, A. (2008). Prediction of Regulatory Elements. In: Keith, J.M. (eds) Bioinformatics. Methods in Molecular Biology™, vol 453. Humana Press. https://doi.org/10.1007/978-1-60327-429-6_11
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DOI: https://doi.org/10.1007/978-1-60327-429-6_11
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