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How do transcription factors select specific binding sites in the genome?

Nature Structural & Molecular Biology volume 16, pages 1118–1120 (2009)Cite this article

How does a transcription factor select a specific DNA response element given the presence of degenerate sequences? To date, this question has largely been viewed from the standpoint of DNA sequence variability and transcription factor binding affinity under steady-state conditions. Here we propose that to address this problem, it is also necessary to account for fluctuating cellular conditions. These lead to dynamic changes in the ensemble of protein (and DNA) conformational states via allosteric effects.

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Figure 1: Schematic illustration of selective binding of transcriptional control proteins to their degenerate response elements under different environmental conditions.
Figure 2: Schematic illustration of the free-energy-landscape shifts associated with the binding of the transcriptional control protein (TC) to various degenerate response elements (RE1, RE2, RE3 and RE4).

References

  1. Riley, T., Sontag, E., Chen, P. & Levine, A. Nat. Rev. Mol. Cell Biol. 9, 402–412 (2008).

    Article  CAS  Google Scholar 

  2. Ma, B., Kumar, S., Tsai, C.J. & Nussinov, R. Protein Eng. 12, 713–720 (1999).

    Article  CAS  Google Scholar 

  3. Kumar, S., Ma, B., Tsai, C.J., Sinha, N. & Nussinov, R. Protein Sci. 9, 10–19 (2000).

    Article  CAS  Google Scholar 

  4. Tsai, C.J., Ma, B. & Nussinov, R. Proc. Natl. Acad. Sci. USA 96, 9970–9972 (1999).

    Article  CAS  Google Scholar 

  5. Lange, O.F. et al. Science 320, 1471–1475 (2008).

    Article  CAS  Google Scholar 

  6. Boehr, D.D. & Wright, P.E. Science 320, 1429–1430 (2008).

    Article  CAS  Google Scholar 

  7. Gunasekaran, K., Ma, B. & Nussinov, R. Proteins 57, 433–443 (2004).

    Article  CAS  Google Scholar 

  8. del Sol, A., Tsai, C.J., Ma, B. & Nussinov, R. Structure 17, 1042–1050 (2009).

    Article  CAS  Google Scholar 

  9. Panne, D. Curr. Opin. Struct. Biol. 18, 236–242 (2008).

    Article  CAS  Google Scholar 

  10. Weinberg, R.L., Veprintsev, D.B., Bycroft, M. & Fersht, A.R. J. Mol. Biol. 348, 589–596 (2005).

    Article  CAS  Google Scholar 

  11. Espinosa, J.M. Oncogene 27, 4013–4023 (2008).

    Article  CAS  Google Scholar 

  12. El Marzouk, S., Gahattamaneni, R., Joshi, S.R. & Scovell, W.M. J. Steroid Biochem. Mol. Biol. 110, 186–195 (2008).

    Article  CAS  Google Scholar 

  13. Chandra, V. et al. Nature 456, 350–356 (2008).

    Article  Google Scholar 

  14. Boehr, D.D., Nussinov, R. & Wright, P.E. Nat. Chem. Biol. 5, 789–796 (2009).

    Article  CAS  Google Scholar 

  15. Ma, B. & Nussinov, R. Proc. Natl. Acad. Sci. USA 106, 6887–6888 (2009).

    Article  CAS  Google Scholar 

  16. Völker, J., Klump, H.H. & Breslauer, K.J. Proc. Natl. Acad. Sci. USA 105, 18326–18330 (2008).

    Article  Google Scholar 

  17. Chaires, J.B. ACS Chem. Biol. 3, 207–209 (2008).

    Article  CAS  Google Scholar 

  18. Thornborrow, E.C. & Manfredi, J.J. J. Biol. Chem. 276, 15598–15608 (2001).

    Article  CAS  Google Scholar 

  19. Sullivan, A. & Lu, X. Br. J. Cancer 96, 196–200 (2007).

    Article  CAS  Google Scholar 

  20. Ahn, J., Byeon, I.J., Byeon, C.H. & Gronenborn, A.M. J. Biol. Chem. 284, 13812–13822 (2009).

    Article  CAS  Google Scholar 

  21. Nagy, L. & Schwabe, J.W. Trends Biochem. Sci. 29, 317–324 (2004).

    Article  CAS  Google Scholar 

  22. Meijsing, S.H. et al. Science 324, 407–410 (2009).

    Article  CAS  Google Scholar 

  23. Tsai, C.J., Del Sol, A. & Nussinov, R. Mol. Biosyst. 5, 207–216 (2009).

    Article  CAS  Google Scholar 

  24. Frauenfelder, H., Sligar, S.G. & Wolynes, P.G. Science 254, 1598–1603 (1991).

    Article  CAS  Google Scholar 

  25. Smock, R.G. & Gierasch, L.M. Science 324, 198–203 (2009).

    Article  CAS  Google Scholar 

  26. Liu, J. & Nussinov, R. PLoS Comput. Biol. 5, e1000527 (2009).

    Article  Google Scholar 

Download references

Acknowledgements

This project was funded in whole or in part with federal funds from the US National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. This research was supported (in part) by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research.

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  1. Yongping Pan, Chung-Jung Tsai, Buyong Ma and Ruth Nussinov are at the Basic Science Program, SAIC-Frederick, Inc., Center for Cancer Research Nanobiology Program, National Cancer Institute–Frederick, Frederick, Maryland, USA.,

    Yongping Pan, Chung-Jung Tsai & Buyong Ma

  2. Department of Human Genetics and Molecular Medicine, Ruth Nussinov is also at the Sackler Institute of Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.,

    Ruth Nussinov

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  1. Yongping Pan
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Correspondence to Ruth Nussinov.

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Pan, Y., Tsai, CJ., Ma, B. et al. How do transcription factors select specific binding sites in the genome?. Nat Struct Mol Biol 16, 1118–1120 (2009). https://doi.org/10.1038/nsmb1109-1118

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