Skip to main content

Prediction of Regulatory Elements

  • Protocol
Bioinformatics

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 453))

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).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Stormo, G. D. (2000) DNA binding sites: representation and discovery.Bioinformatics 16, 16–23.

    Article  PubMed  CAS  Google Scholar 

  2. Wasserman, W. W., Sandelin, A. (2004) Applied bioinformatics for the identification of regulatory elements.Nat Rev Genet 5, 276–287.

    Article  PubMed  CAS  Google Scholar 

  3. Fickett, J. W. (1996) Quantitative discrimination of MEF2 sites.Mol Cell Biol 16,437–441.

    PubMed  CAS  Google Scholar 

  4. Wasserman, W. W., Fickett, J. W. (1998) Identification of regulatory regions which confer muscle-specific gene expression.J Mol Biol 278, 167–181.

    Article  PubMed  CAS  Google Scholar 

  5. Lenhard,B.,Sandelin,A.,Mendoza,L.,et al. (2003) Identification of conserved regulatory elements by comparative genome analysis.j Biol 2, 13.

    Article  PubMed  Google Scholar 

  6. Wasserman, W. W., Palumbo, M., Thompson, W., et al. (2000) Human-mouse genome comparisons to locate regulatory sites.Nat Genet 26, 225–228.

    Article  PubMed  CAS  Google Scholar 

  7. Alberts, B., Johnson, A., Lewis, J., et al. (2002)Molecular Biology of the Cell. Garland Publishing, New York.

    Google Scholar 

  8. Kadonaga, J. T. (2004) Regulation of RNA polymerase II transcription by sequence-specific DNA binding factors.Cell 116, 247–257.

    Article  PubMed  CAS  Google Scholar 

  9. Lewin, B. (2004)Genes VIII. Pearsson Education, New York.

    Google Scholar 

  10. 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.

    PubMed  CAS  Google Scholar 

  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, D95–97.

    Article  PubMed  CAS  Google Scholar 

  12. 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.

    Article  PubMed  CAS  Google Scholar 

  13. Lenhard, B., Wasserman, W W (2002) TFBS: Computational framework for transcription factor binding site analysis.Bioinformatics 18, 1135–1136.

    Article  PubMed  CAS  Google Scholar 

  14. 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.

    Article  PubMed  CAS  Google Scholar 

  15. Pollock, R, Treisman, R (1990) A sensitive method for the determination of protein-DNA binding specificities.Nucleic Acids Res 18, 6197–6204.

    Article  PubMed  CAS  Google Scholar 

  16. Rice, P., Longden, I., Bleasby, A. (2000) EMBOSS: the European Molecular Biology Open Software Suite.Trends Genet 16, 276–277.

    Article  PubMed  CAS  Google Scholar 

  17. Durbin, R, Eddy, S. R., Krogh, A., et al. (2001)Biological Sequence Analysis. Cambridge Press, Cambridge, UK.

    Google Scholar 

  18. Schneider, T. D., Stephens, R M. (1990) Sequence logos: a new way to display consensus sequences.Nucleic Acids Res 18, 6097–7100.

    Article  PubMed  CAS  Google Scholar 

  19. 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.

    PubMed  CAS  Google Scholar 

  20. 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.

    Google Scholar 

  21. Hinrichs, A. S., Karolchik, D., Baertsch, R., et al. (2006) The UCSC Genome Browser Database: update 2006.Nucleic Acids Res 34, D590–598.

    Article  PubMed  CAS  Google Scholar 

  22. 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.

    Article  PubMed  CAS  Google Scholar 

  23. Carninci, P., Kasukawa, T, Katayama, S., et al. (2005) The transcriptional landscape of the mammalian genome.Science 309, D556–561.

    Google Scholar 

  24. Birney, E., Andrews, D., Caccamo, M.,et al. (2006) Ensembl 2006.Nucleic Acids Res 34, D556–561.

    Article  PubMed  CAS  Google Scholar 

  25. Carninci, P., Sandelin, A., Lenhard, B., et al. (2006) Genome-wide analysis of mammalian promoter architecture and evolution,Nat Genet 38, 626–635.

    Article  PubMed  CAS  Google Scholar 

  26. 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.

    Article  PubMed  CAS  Google Scholar 

  27. Schwartz, S., Kent, W J., Smit, A., et al. (2003) Human-mouse alignments with BLASTZ.Genome Res 13,103–107.

    Article  PubMed  CAS  Google Scholar 

  28. Blanchette, M., Kent, W. J., Riemer, C, et al. (2004) Aligning multiple genomic sequences with the threaded blockset aligner.Genome Res 14, 708–715.

    Article  PubMed  CAS  Google Scholar 

  29. Altschul, S. F, Gish, W., Miller, W., et al. (1990) Basic local alignment search tool.J Mol Biol 215, 403–410.

    PubMed  CAS  Google Scholar 

  30. 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.

    PubMed  Google Scholar 

  31. Puig, O., Tjian, R. (2005) Transcriptional feedback control of insulin receptor by dFOXO/ FOXO1.Genes Dev 19, 2435–2446.

    Article  PubMed  CAS  Google Scholar 

  32. Koonin, E. V. (2005) Orthologs, paralogs, and evolutionary genomics.Annu Rev Genet 39, 309–338.

    Article  PubMed  CAS  Google Scholar 

  33. 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.

    PubMed  CAS  Google Scholar 

  34. Frith, M., Ponjavic, J., Fredman, D., et al. (2006) Evolutionary turnover of mammalian transcription start sites.Genome Res 16, 713–722.

    Article  PubMed  CAS  Google Scholar 

  35. 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.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Thanks to Ann Karlsson for comments on the text.

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Humana Press, a part of Springer Science+Business Media, LLC

About this protocol

Cite this protocol

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

Download citation

  • DOI: https://doi.org/10.1007/978-1-60327-429-6_11

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-60327-428-9

  • Online ISBN: 978-1-60327-429-6

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics