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When activators repress and repressors activate: a qualitative analysis of the Shea-Ackers model. (English) Zbl 1166.92021

Summary: The concept of activation in transcriptional regulation is based on the assumption that product mRNA increases monotonically as a function of regulator concentration. We analyze the M. Shea and G. Ackers model [J. Mol. Biol. 181, 211–230 (1985)] of transcription and find this assumption to be correct only for the simplest of promoters. We define a new regulatory constant that is a nonlinear combination of association and transcription initiation constants characterizing activation and repression for more complicated promoters. Our results can guide the synthesis of new promoters and lead to a deeper understanding of the constraints guiding the natural promoters evolution.

MSC:

92C40 Biochemistry, molecular biology
37N25 Dynamical systems in biology
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[1] Ackers, G., Johnson, A., Shea, M., 1982. Qualitative model for gene regulation by {\(\lambda\)} phage repressor. Proc. Natl. Acad. Sci. 79, 1129–1133.
[2] Alon, U., 2007. An Introduction to Systems Biology. Chapman & Hall/CRC, London/Boca Raton.
[3] Angeli, D., Ferrell, J., Sontag, E., 2004. Detection of multistability, bifurcations, and hysteresis in a large class of biological positive-feedback systems. Proc. Natl. Acad. Sci. 101, 1822–1827.
[4] Bintu, L., Buchler, N., Garcia, H., Gerland, U., Hwa, T., et al., 2002. Transcriptional regulation by the numbers: models. Curr. Opin. Genet. Dev. 15, 116–124.
[5] Bremer, H., Dennis, P., 1996. Modulation of chemical composition and other parameters of the cell by growth rate. In: FN, et al. (Eds.), In Escherichia coli and Salmonella thyphymurium: Cellular and Molecular Biology, vol. 2.
[6] Busby, S., Ebright, R., 1999. Transcription activation by catabolite activator protein (CAP). J. Mol. Biol. 293, 199–213.
[7] Elowitz, M., Leibler, S., 2000. A synthetic oscillatory network of transcriptional regulators. Nature 403, 335–338.
[8] Gardner, T., Cantor, C., Collins, J., 2000. Construction of a genetic toggle switch in Escherichia coli. Nature 403, 339–342.
[9] Gedeon, T., 1998. Cyclic Feedback Systems. Memoirs of AMS, vol. 637. Americal Mathematical Society, Providence. · Zbl 0991.34051
[10] Gedeon, T., Mischaikow, K., Patterson, K., Traldi, E., 2008. Binding cooperativity in phage {\(\lambda\)} is not sufficient to produce an effective switch. Biophys. J. 94, 3384–3392.
[11] Hawley, D., McClure, W., 1983. The effect of a lambda repressor mutation on the activation of transcription initiation from the lambda p RM promoter. Cell 32, 327–333.
[12] Hill, T., 1960. Introduction to Statistical Thermodynamics. Addison–Wesley, Reading. · Zbl 0201.52404
[13] Lanzer, M., Bujard, H., 1988. Promoters largely determine the efficiency of repressor. Proc. Natl. Acad. Sci. 85, 8973–8977.
[14] Lartigue, C., Glass, J., Alperovich, N., Pieper, R., Parmar, P., et al., 2007. Genome transplantation in bacteria: changing one species to another. Science 317, 632–638.
[15] Li, M., McClure, W.R., Susskind, M., 1997. Changing the mechanism of transcriptional activation by phage {\(\lambda\)} repressor. Proc. Natl. Acad. Sci. 94, 3691–3696.
[16] Lutz, R., Bujard, H., 1997. Independent and tight regulation of transcriptional units in Escherishia coli via the LacR/O, the TetR/O and AraC/I1-I2 regulatory elements. Nucleic Acids Res. 25, 1203–1210.
[17] Mallet-Paret, J., Smith, H., 1990. The Poincaré-Bendixson theorem for monotone feedback systems. J. Dyn. Differ. Equ. 2, 367–421. · Zbl 0712.34060
[18] Nöllman, M., Crisona, N.J., Arimondo, P., 2007. Thirty years of Escherichia coli DNA gyrase: from in vivo function to single-molecule mechanism. Biochimie 89, 490–499.
[19] Ptashne, M., 2004. A Genetic Switch. Cold Spring Harbor Laboratory Press, Cold Spring Harbor.
[20] Ptashne, M., Gann, A., 2001. Genes and Signals. Cold Spring Harbor Laboratory Press, Cold Spring Harbor.
[21] Santillán, M., Mackey, M., 2004a. Why the lysogenic state of phage {\(\lambda\)} is so stable: a mathematical modeling approach. Biophys. J. 86, 75–84.
[22] Santillán, M., Mackey, M., 2004b. Influence of catabolite repression and inducer exclusion on the bistable behavior of the lac operon. Biophys. J. 86, 1282–1292.
[23] Schneider, R., Travers, A., Kuteleladze, T., Muskhelishvili, G., 1999. A DNA architectural protein couples cellular physiology and DNA topology in Escherichia coli. Mol. Microbiol. 35, 953–964.
[24] Schroder, O., Wagner, R., 2000. The bacterial DNA-binding protein H-NS represses ribosomal RNA transcription by trapping RNA polymerase in the initiation complex. J. Mol. Biol. 298, 737–747.
[25] Shea, M., Ackers, G., 1985. The O R control system of bacteriophage lambda: a physical-chemical model for gene regulation. J. Mol. Biol. 181, 211–230.
[26] Snyder, L., Champness, W., 2003. Molecular Biology of Bacteria. ASM Press, Materials Park.
[27] Watson, J., Baker, T., Bell, S., Gann, A., Levine, M. et al., 2003. Molecular Biology of the Gene. Benjamin–Cummings, Redwood City.
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