Skip to main content
SpringerLink
Log in

Regulatory Regions in DNA: Promoters, Enhancers, Silencers, and Insulators

  • Protocol
  • First Online:
Computational Biology of Transcription Factor Binding

Part of the book series: Methods in Molecular Biology ((MIMB,volume 674))

Abstract

One of the mechanisms through which protein levels in the cell are controlled is through transcriptional regulation. Certain regions, called cis-regulatory elements, on the DNA are footprints for the trans-acting proteins involved in transcription, either for the positioning of the basic transcriptional machinery or for the regulation – in simple terms turn on or turn off – thereof. The basic transcriptional machinery is DNA-dependent RNA polymerase (RNAP) which synthesizes various types of RNA and core promoters on the DNA are used to position the RNAP. Other nearby regions will regulate the transcription: in prokaryotic organisms operators are involved; in eukaryotic organisms, proximal promoter regions, enhancers, silencers, and insulators are present. This chapter will describe the various DNA regions involved in transcription and transcriptional regulation.

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

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
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. Levine, M., and Tjian, R. (2003) Transcriptional regulation and animal diversity, Nature 424, 147–151.

    Article  PubMed  CAS  Google Scholar 

  2. Yanofsky, C. (2004) The different roles of tryptophan transfer RNA in regulating trp operon expression in E. coli versus B. subtilis. Trends Genet 20(8), 367–374.

    Article  PubMed  CAS  Google Scholar 

  3. Ptashne, M., Backmann, K., Humayun, M.Z. et al. (1976) Autoregulation and function of a repressor in bacteriophage Lambda. Science 194, 156–161.

    Article  PubMed  CAS  Google Scholar 

  4. Malan, T.P., and McClure, W.R. (1984) Dual promoter control of the Escherichia coli lactose operon. Cell 39(1), 173–180.

    Article  PubMed  CAS  Google Scholar 

  5. Struhl, K., Kadosh, D., Keaveney, M. et al. (1998) Activation and repression mechanisms in yeast. Cold Spring Harb Symp Quant Biol 63, 413–421.

    Article  PubMed  CAS  Google Scholar 

  6. Cooper, S.J., Trinklein, N.D., Anton, E.D. et al. (2006) Comprehensive analysis of transcriptional promoter structure and function in 1% of the human genome. Genome Res 16, 1–10.

    Article  PubMed  CAS  Google Scholar 

  7. Gershenzon, N.I., and Ioshikhes, I.P. (2005) Synergy of human Pol II core promoter elements revealed by statistical sequence analysis. Bioinformatics 21, 1295–1300.

    Article  PubMed  CAS  Google Scholar 

  8. Sandelin, A., Carninci, P., Lenhard, B. et al. (2007) Mammalian RNA polymerase II core promoters: insights from genome-wide studies. Nature Genet 8, 424–436.

    CAS  Google Scholar 

  9. Carninci, P., Kasukawa, T., Katayama, S. et al. (2005) The transcriptional landscape of the mammalian genome. Science 309, 1559–1563.

    Article  PubMed  CAS  Google Scholar 

  10. Carninci, P., Sandelin, A., Lenhard, B. et al. (2006) Genome-wide analysis of mammalian promoter architecture and evolution. Nature Genet 38(6), 626–635.

    Article  PubMed  CAS  Google Scholar 

  11. Juven-Gershon, T., Hsu, J., Theisen, J.W.M. et al. (2008) The RNA polymerase II core promoter – the gateway to transcription. Curr Opin Cell Biol 20, 253–259.

    Article  PubMed  CAS  Google Scholar 

  12. Reeve, J.N. (2003) Archaeal chromatin and transcription. Mol Microbiol 48, 587–598.

    Article  PubMed  CAS  Google Scholar 

  13. Molina, C., and Grotewold, E. (2005) Genome wide analysis of Arabidopsis core promoters. BMC Genomics 6, 25.

    Article  PubMed  Google Scholar 

  14. Yamamoto, Y.Y., Ichida, H., Abe, T. et al. (2007) Differentiation of core promoter architecture between plants and mammals revealed by LDSS analysis. Nucleic Acids Res 35, 6219–6226.

    Article  PubMed  CAS  Google Scholar 

  15. Ponjavic, J., Lenhard, B., Kai, C. et al. (2006) Transcriptional and structural impact of TATA-initiation site spacing in mammalian core promoters. Genome Biol 7, R78.

    Article  PubMed  Google Scholar 

  16. Hahn, S. (2004) Structure and mechanism of the RNA polymerase II transcription machinery. Nat Struct Mol Biol 11, 394–403.

    Article  PubMed  CAS  Google Scholar 

  17. Yang, C., Bolotin, E., Jiang, T. et al. (2007) Prevalence of the initiator over the TATA box in human and yeast genes and identification of DNA motifs enriched in human TATA-less core promoters. Gene 1;389(1), 52–65.

    Article  Google Scholar 

  18. Lagrange, T., Kapanidis, A.N., Tang, H. et al. (1998) New core promoter element in RNA polymerase II-dependent transcription: sequence-specific DNA binding by transcription factor IIB. Genes Dev 12, 34–44.

    Article  PubMed  CAS  Google Scholar 

  19. Deng, W., and Roberts, S.G. (2005) A core promoter element downstream of the TATA box that is recognized by TFIIB. Genes Dev 19, 2418–2423.

    Article  PubMed  CAS  Google Scholar 

  20. Deng, W., and Roberts, S.G. (2007) TFIIB and the regulation of transcription by RNA polymerase II. Chromosoma 116, 417–429.

    Article  PubMed  CAS  Google Scholar 

  21. Gershenzon, N.I., Trifonov, E.N., and Ioshikhes, I.P. (2006) The features of Drosophila core promoters revealed by statistical analysis. BMC Genomics 7, 161.

    Article  PubMed  Google Scholar 

  22. Kutach, A.K., and Kadonaga, J.T. (2000) The downstream promoter element DPE appears to be as widely used as the TATA box in Drosophila core promoters. Mol Cell Biol 20, 4754–4764.

    Article  PubMed  CAS  Google Scholar 

  23. Burke, T.W., and Kadonaga, J.T. (1996) Drosophila TFIID binds to a conserved downstream basal promoter element that is present in many TATA-box-deficient promoters. Genes Dev 10, 711–724.

    Article  PubMed  CAS  Google Scholar 

  24. Lim, C.Y., Santoso, B., Boulay, T. et al. (2004) The MTE, a new core promoter element for transcription by RNA polymerase II. Genes Dev 18, 1606–1617.

    Article  PubMed  CAS  Google Scholar 

  25. Lewis, B.A., Kim, T.K., and Orkin, S.H. (2000) A downstream element in the human beta-globin promoter: evidence of extended sequence-specific transcription factor IID contacts. Proc Natl Acad Sci USA 97, 7172–7177.

    Article  PubMed  CAS  Google Scholar 

  26. Tokusumi, Y., Ma, Y., Song, X. et al. (2007) The new core promoter element XCPE1 (X Core Promoter Element 1) directs activator-, mediator-, and TATA-binding protein-dependent but TFIID-independent RNA polymerase II transcription from TATA-less promoters. Mol Cell Biol 27, 1844–1858.

    Article  PubMed  CAS  Google Scholar 

  27. Su, W., Jackson, S., Tjian, R. et al. (1991) DNA looping between sites for transcriptional activation: self-association of DNA-bound Sp1. Genes Dev 5, 820–826.

    Article  PubMed  CAS  Google Scholar 

  28. Calhoun, V.C., Stathopoulos, A., and Levine, M. (2002) Promoter-proximal tethering elements regulate enhancer-promoter specificity in the Drosophila Antennapedia complex. Proc Natl Acad Sci USA 99, 9243–9247.

    Article  PubMed  CAS  Google Scholar 

  29. Birney, E., Stamatoyannopoulos, J.A., Dutta, A. et al. (2007) Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447, 799–816.

    Article  PubMed  CAS  Google Scholar 

  30. Latchman, D.S. (2008) Eukaryotic transcription factors (5th edn). Academic Press, London.

    Google Scholar 

  31. Fullwood, M.J., and Ruan, Y. (2009) ChIP-based methods for the identification of long-range chromatin interactions. J Cell Biochem 107, 30–39.

    Article  PubMed  CAS  Google Scholar 

  32. Lieberman-Aiden, E., van Berkum, N.L., Williams, L. et al. (2009) Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326, 289–293.

    Article  PubMed  CAS  Google Scholar 

  33. Marenduzzo, D., Faro-Trindade, I., and Cook, P.R. (2007) What are the molecular ties that maintain genomic loops? Trends Genet 23, 126–133.

    Article  PubMed  CAS  Google Scholar 

  34. Miele, A., and Dekker, J. (2008) Long-range chromosomal interactions and gene regulation. Mol Biosyst 4, 1046–1057.

    Article  PubMed  CAS  Google Scholar 

  35. Gazner, M., and Felsenfeld, G. (2006) Insulators: exploiting transcriptional and epigenetic mechanisms. Nat Genet 7, 703–713.

    Google Scholar 

  36. Nobrega, M.A., Ovcharenko, I., Afzal, V. et al. (2003) Scanning human gene deserts for long-range enhancers. Science 302, 413.

    Article  PubMed  CAS  Google Scholar 

  37. Siepel, A., Bejerano, G., Pedersen, J.S. et al. (2005) Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res 15, 1034–1050.

    Article  PubMed  CAS  Google Scholar 

  38. Visel, A., Rubin, E.M., and Pennacchio, L.A. (2009) Genomic views of distant-acting enhancers. Nature 461, 199–205.

    Article  PubMed  CAS  Google Scholar 

  39. Lettice, L.A., Hill, A.E., Devenney, P.S. et al. (2008) Point mutations in a distant sonic hedgehog cis-regulator generate a variable regulatory output responsible for preaxial polydactyly. Hum Mol Genet 17, 978–985.

    Article  PubMed  CAS  Google Scholar 

  40. Lettice, L.A., Horikoshi, T., Heaneya, S.J.H. et al. (2002) Disruption of a long-range cis-acting regulator for Shh causes preaxial polydactyly. Proc Natl Acad Sci USA 99, 7548–7553.

    Article  PubMed  CAS  Google Scholar 

  41. de Bruin, D., Zaman, Z., Liberatore, R.A. et al. (2001) Telomere looping permits gene activation by a downstream UAS in yeast. Nature 409, 109–113.

    Article  PubMed  Google Scholar 

  42. Campbell, R.N., Leverentz, M.K., Ryan, L.A. et al. (2008) Metabolic control of transcription: paradigms and lessons from Saccharomyces cerevisiae. Biochem J 414, 177–187.

    Article  PubMed  CAS  Google Scholar 

  43. Ogbourne, S., and Antalis, T.M. (1998) Transcriptional control and the role of silencers in transcriptional regulation in eukaryotes. Biochemistry 331, 1–14.

    CAS  Google Scholar 

  44. Holdridge, C., and Dorsett, D. (1991) Repression of hsp70 heat shock gene transcription by the suppressor of hairy-wing protein of Drosophila melanogaster. Mol Cell Biol 11, 1894–1900.

    PubMed  CAS  Google Scholar 

  45. Bell, A.C., West, A.G., and Felsenfeld, G. (1999) The protein CTCF is required for the enhancer blocking activity of vertebrate insulators. Cell 98, 387–396.

    Article  PubMed  CAS  Google Scholar 

  46. Smale, S.T., and Baltimore, D. (1989) The “initiator” as a transcription control element. Cell 57, 103–113.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The author is partly supported through the National Science Foundation grant EPSCoR EPS-0701892.

Author information

Authors and Affiliations

  1. Bioinformatics Core Research Facility, Center for Biotechnology and School for Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, USA

    Jean-Jack M. Riethoven

Authors
  1. Jean-Jack M. Riethoven
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jean-Jack M. Riethoven .

Editor information

Editors and Affiliations

  1. , Department of Statistics, University of Nebraska-Lincoln, Vine Street 1901, Lincoln, 68588-0665, Nebraska, USA

    Istvan Ladunga

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Riethoven, JJ.M. (2010). Regulatory Regions in DNA: Promoters, Enhancers, Silencers, and Insulators. In: Ladunga, I. (eds) Computational Biology of Transcription Factor Binding. Methods in Molecular Biology, vol 674. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-854-6_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-60761-854-6_3

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-853-9

  • Online ISBN: 978-1-60761-854-6

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation