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Non-linear Dynamics in Transcriptional Regulation: Biological Logic Gates

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Nonlinear Dynamics in Biological Systems

Part of the book series: SEMA SIMAI Springer Series ((SEMA SIMAI,volume 7))

Abstract

Gene expression relies on the interaction of numerous transcriptional signals at the promoter to elicit a response—to read or not to read the genomic code, and if read, the strength of the read. The interplay of transcription factors can be viewed as nonlinear dynamics underlying the biological complexity. Here we analyse the regulation of the cyclooxygenase 2 promoter by NF-κB using thermostatistical and quantitative kinetic modelling and propose the presence of a genetic Boolean AND logic gate controlling the differential expression of cyclooxygenase 2 among species.

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References

  1. Venter, J.C., Adams, M.D., Myers, E.W., Li, P.W., Mural, R.J., et al.: The sequence of the human genome. Science 291, 1304–1351 (2001)

    Article  ADS  Google Scholar 

  2. Lander, E.S., Linton, L.M., Birren, B., Nusbaum, C., Zody, M.C., et al.: Initial sequencing and analysis of the human genome. Nature 409, 860–921 (2001)

    Article  ADS  Google Scholar 

  3. Okamoto, A., Tanaka, K., Saito, I.: DNA logic gates. J. Am. Chem. Soc. 126, 9458–9463 (2004)

    Article  Google Scholar 

  4. Goldman, N., Bertone, P., Chen, S., Dessimoz, C., LeProust, E.M., et al.: Towards practical, high-capacity, low-maintenance information storage in synthesized DNA. Nature 494, 77–80 (2013)

    Article  ADS  Google Scholar 

  5. Fisher, J., Henzinger, T.A.: Executable cell biology. Nat. Biotechnol. 25, 1239–1249 (2007)

    Article  Google Scholar 

  6. Kunst, F., Ogasawara, N., Moszer, I., Albertini, A.M., Alloni, G., et al.: The complete genome sequence of the gram-positive bacterium Bacillus subtilis. Nature 390, 249–256 (1997)

    Article  ADS  Google Scholar 

  7. Gibson, D.G., Glass, J.I., Lartigue, C., Noskov, V.N., Chuang, R.Y., et al.: Creation of a bacterial cell controlled by a chemically synthesized genome. Science 329, 52–56 (2010)

    Article  ADS  Google Scholar 

  8. Wan, F., Lenardo, M.J.: Specification of DNA binding activity of NF-kappaB proteins. Cold Spring Harb. Perspect. Biol. 1, a000067 (2009)

    Article  Google Scholar 

  9. Wong, D., Teixeira, A., Oikonomopoulos, S., Humburg, P., Lone, I.N., et al.: Extensive characterization of NF-kappaB binding uncovers non-canonical motifs and advances the interpretation of genetic functional traits. Genome Biol. 12, R70 (2011)

    Article  Google Scholar 

  10. Fedorova, L., Fedorov, A.: Introns in gene evolution. Genetica 118, 123–131 (2003)

    Article  Google Scholar 

  11. Matlin, A.J., Clark, F., Smith, C.W.: Understanding alternative splicing: towards a cellular code. Nat. Rev. Mol. Cell Biol. 6, 386–398 (2005)

    Article  Google Scholar 

  12. Black, D.L.: Mechanisms of alternative pre-messenger RNA splicing. Annu. Rev. Biochem. 72, 291–336 (2003)

    Article  Google Scholar 

  13. Modrek, B., Lee, C.: A genomic view of alternative splicing. Nat. Genet. 30, 13–19 (2002)

    Article  Google Scholar 

  14. Mockler, T.C., Chan, S., Sundaresan, A., Chen, H., Jacobsen, S.E., et al.: Applications of DNA tiling arrays for whole-genome analysis. Genomics 85, 1–15 (2005)

    Article  Google Scholar 

  15. Wang, Z., Gerstein, M., Snyder, M.: RNA-Seq: a revolutionary tool for transcriptomics. Nat. Rev. Genet. 10, 57–63 (2009)

    Article  Google Scholar 

  16. Cavadas, M.A.S., Cheong, A.: Monitoring of transcriptional dynamics of HIF and NF kappa B activities. Bioluminescent Imaging Methods Protoc. 1098, 97–105 (2014)

    Article  Google Scholar 

  17. Carey, M., Lin, Y.S., Green, M.R., Ptashne, M.: A mechanism for synergistic activation of a mammalian gene by GAL4 derivatives. Nature 345, 361–364 (1990)

    Article  ADS  Google Scholar 

  18. Bruning, U., Fitzpatrick, S.F., Frank, T., Birtwistle, M., Taylor, C.T., et al.: NFkappaB and HIF display synergistic behaviour during hypoxic inflammation. Cell. Mol. Life Sci. 69, 1319–1329 (2012)

    Article  Google Scholar 

  19. Rossi, F.M., Kringstein, A.M., Spicher, A., Guicherit, O.M., Blau, H.M.: Transcriptional control: rheostat converted to on/off switch. Mol. Cell 6, 723–728 (2000)

    Article  Google Scholar 

  20. Nguyen, L.K., Cavadas, M.A., Kholodenko, B.N., Frank, T.D., Cheong, A.: Species differential regulation of COX2 can be described by an NFkappaB-dependent logic AND gate. Cell. Mol. Life Sci. 72, 2431–2443 (2015)

    Article  Google Scholar 

  21. Biggar, S.R., Crabtree, G.R.: Cell signaling can direct either binary or graded transcriptional responses. EMBO J. 20, 3167–3176 (2001)

    Article  Google Scholar 

  22. Joers, A., Jaks, V., Kase, J., Maimets, T.: p53-dependent transcription can exhibit both on/off and graded response after genotoxic stress. Oncogene 23, 6175–6185 (2004)

    Article  Google Scholar 

  23. Ertel, A., Tozeren, A.: Human and mouse switch-like genes share common transcriptional regulatory mechanisms for bimodality. BMC Genom. 9, 628 (2008)

    Article  Google Scholar 

  24. Ertel, A., Tozeren, A.: Switch-like genes populate cell communication pathways and are enriched for extracellular proteins. BMC Genom. 9, 3 (2008)

    Article  Google Scholar 

  25. Nguyen, L.K., Cavadas, M.A., Scholz, C.C., Fitzpatrick, S.F., Bruning, U., et al.: A dynamic model of the hypoxia-inducible factor 1-alpha (HIF-1alpha) network. J. Cell Sci. 126, 1454–63 (2013)

    Article  Google Scholar 

  26. Leung, T.H., Hoffmann, A., Baltimore, D.: One nucleotide in a kappaB site can determine cofactor specificity for NF-kappaB dimers. Cell 118, 453–464 (2004)

    Article  Google Scholar 

  27. Li, J., Schmidt, A.M.: Characterization and functional analysis of the promoter of RAGE, the receptor for advanced glycation end products. J. Biol. Chem. 272, 16498–16506 (1997)

    Article  Google Scholar 

  28. Ohmori, Y., Hamilton, T.A.: Cooperative interaction between interferon (IFN) stimulus response element and kappa B sequence motifs controls IFN gamma- and lipopolysaccharide-stimulated transcription from the murine IP-10 promoter. J. Biol. Chem. 268, 6677–6688 (1993)

    Google Scholar 

  29. Fiering, S., Northrop, J.P., Nolan, G.P., Mattila, P.S., Crabtree, G.R., et al.: Single cell assay of a transcription factor reveals a threshold in transcription activated by signals emanating from the T-cell antigen receptor. Genes Dev. 4, 1823–1834 (1990)

    Article  Google Scholar 

  30. Lin, Y.S., Carey, M., Ptashne, M., Green, M.R.: How different eukaryotic transcriptional activators can cooperate promiscuously. Nature 345, 359–361 (1990)

    Article  ADS  Google Scholar 

  31. Weintraub, H.: Assembly and propagation of repressed and depressed chromosomal states. Cell 42, 705–711 (1985)

    Article  Google Scholar 

  32. Santos-Rosa, H., Schneider, R., Bannister, A.J., Sherriff, J., Bernstein, B.E., et al.: Active genes are tri-methylated at K4 of histone H3. Nature 419, 407–411 (2002)

    Article  ADS  Google Scholar 

  33. Margueron, R., Trojer, P., Reinberg, D.: The key to development: interpreting the histone code? Curr. Opin. Genet. Dev. 15, 163–176 (2005)

    Article  Google Scholar 

  34. Kurdistani, S.K.: Histone modifications as markers of cancer prognosis: a cellular view. Br. J. Cancer 97, 1–5 (2007)

    Article  Google Scholar 

  35. Nguyen, L.K., Munoz-Garcia, J., Maccario, H., Ciechanover, A., Kolch, W., et al.: Switches, excitable responses and oscillations in the Ring1B/Bmi1 ubiquitination system. PLoS Comput. Biol. 7, e1002317 (2011)

    Article  ADS  Google Scholar 

  36. Seok, J., Warren, H.S., Cuenca, A.G., Mindrinos, M.N., Baker, H.V., et al.: Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc. Natl. Acad. Sci. U. S. A. 110, 3507–3512 (2013)

    Article  ADS  Google Scholar 

  37. Cheng, Y., Ma, Z., Kim, B.H., Wu, W., Cayting, P., et al.: Principles of regulatory information conservation between mouse and human. Nature 515, 371–375 (2014)

    Article  ADS  Google Scholar 

  38. Lin, S., Lin, Y., Nery, J.R., Urich, M.A., Breschi, A., et al.: Comparison of the transcriptional landscapes between human and mouse tissues. Proc. Natl. Acad. Sci. U. S. A. 111, 17224–17229 (2014)

    Article  ADS  Google Scholar 

  39. Wittkopp, P.J., Kalay, G.: Cis-regulatory elements: molecular mechanisms and evolutionary processes underlying divergence. Nat. Rev. Genet. 13, 59–69 (2012)

    Article  Google Scholar 

  40. Ackers, G.K., Johnson, A.D., Shea, M.A.: Quantitative model for gene regulation by lambda phage repressor. Proc. Natl. Acad. Sci. U. S. A. 79, 1129–1133 (1982)

    Article  ADS  Google Scholar 

  41. Wang, J., Ellwood, K., Lehman, A., Carey, M.F., She, Z.S.: A mathematical model for synergistic eukaryotic gene activation. J. Mol. Biol. 286, 315–325 (1999)

    Article  Google Scholar 

  42. Buchler, N.E., Gerland, U., Hwa, T.: On schemes of combinatorial transcription logic. Proc. Natl. Acad. Sci. U. S. A. 100, 5136–5141 (2003)

    Article  ADS  Google Scholar 

  43. Segal, E., Raveh-Sadka, T., Schroeder, M., Unnerstall, U., Gaul, U.: Predicting expression patterns from regulatory sequence in Drosophila segmentation. Nature 451, 535–540 (2008)

    Article  ADS  Google Scholar 

  44. Dresch, J.M., Liu, X., Arnosti, D.N., Ay, A.: Thermodynamic modeling of transcription: sensitivity analysis differentiates biological mechanism from mathematical model-induced effects. BMC Syst. Biol. 4, 142 (2010)

    Article  Google Scholar 

  45. Frank, T.D., Carmody, A.M., Kholodenko, B.N.: Versatility of cooperative transcriptional activation: a thermodynamical modeling analysis for greater-than-additive and less-than-additive effects. PLoS One 7, e34439 (2012)

    Article  ADS  Google Scholar 

  46. Shea, M.A., Ackers, G.K.: The OR control system of bacteriophage lambda. A physical-chemical model for gene regulation. J. Mol. Biol. 181, 211–230 (1985)

    Google Scholar 

  47. Frank, T.D., Cheong, A., Okada-Hatakeyama, M., Kholodenko, B.N.: Catching transcriptional regulation by thermostatistical modeling. Phys. Biol. 9, 045007 (2012)

    Article  ADS  Google Scholar 

  48. Bintu, L., Buchler, N.E., Garcia, H.G., Gerland, U., Hwa, T., et al.: Transcriptional regulation by the numbers: applications. Curr. Opin. Genet. Dev. 15, 125–135 (2005)

    Article  Google Scholar 

  49. Bintu, L., Buchler, N.E., Garcia, H.G., Gerland, U., Hwa, T., et al.: Transcriptional regulation by the numbers: models. Curr. Opin. Genet. Dev. 15, 116–124 (2005)

    Article  Google Scholar 

  50. Kulasiri, D., Nguyen, L.K., Samarasinghe, S., Xie, Z.: A review of systems biology perspective on genetic regulatory networks with examples. Curr. Bioinform. 3, 197–225 (2008)

    Article  Google Scholar 

  51. Smolen, P., Baxter, D.A., Byrne, J.H.: Modeling transcriptional control in gene networks–methods, recent results, and future directions. Bull. Math. Biol. 62, 247–292 (2000)

    Article  MATH  Google Scholar 

  52. De Jong, H.: Modeling and simulation of genetic regulatory systems: a literature review. J. Comput. Biol. 9, 67–103 (2002)

    Article  Google Scholar 

  53. Chen, T., He, H.L., Church, G.M.: Modeling gene expression with differential equations. Pac. Symp. Biocomput. 4, 29–40 (1999)

    Google Scholar 

  54. Babu, M.M., Luscombe, N.M., Aravind, L., Gerstein, M., Teichmann, S.A.: Structure and evolution of transcriptional regulatory networks. Curr. Opin. Struct. Biol. 14, 283–291 (2004)

    Article  Google Scholar 

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Author information

Authors and Affiliations

  1. Center for the Ecological Study of Perception and Action, University of Connecticut, Storrs, CT, 06269, USA

    Till D. Frank

  2. Instituto Gulbenkian de Ciencia, Rua da Quinta Grande, 2780-156, Oeiras, Portugal

    Miguel A. S. Cavadas

  3. Systems Biology Ireland, University College Dublin, Dublin 4, Ireland

    Lan K. Nguyen

  4. Life and Health Science, Aston University, Birmingham, B4 7ET, UK

    Alex Cheong

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  1. Till D. Frank
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  2. Miguel A. S. Cavadas
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  3. Lan K. Nguyen
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  4. Alex Cheong
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Corresponding author

Correspondence to Alex Cheong .

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Editors and Affiliations

  1. Université Libre de Bruxelles, Brussels, Brussels Hoofdst.ge., Belgium

    Jorge Carballido-Landeira

  2. Basque Center for Applied Mathematics, Bilbao, Spain

    Bruno Escribano

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Frank, T.D., Cavadas, M.A.S., Nguyen, L.K., Cheong, A. (2016). Non-linear Dynamics in Transcriptional Regulation: Biological Logic Gates. In: Carballido-Landeira, J., Escribano, B. (eds) Nonlinear Dynamics in Biological Systems. SEMA SIMAI Springer Series, vol 7. Springer, Cham. https://doi.org/10.1007/978-3-319-33054-9_3

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