全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...
PLOS ONE  2011 

A Simple Negative Interaction in the Positive Transcriptional Feedback of a Single Gene Is Sufficient to Produce Reliable Oscillations

DOI: 10.1371/journal.pone.0027414

Full-Text   Cite this paper   Add to My Lib

Abstract:

Negative and positive transcriptional feedback loops are present in natural and synthetic genetic oscillators. A single gene with negative transcriptional feedback needs a time delay and sufficiently strong nonlinearity in the transmission of the feedback signal in order to produce biochemical rhythms. A single gene with only positive transcriptional feedback does not produce oscillations. Here, we demonstrate that this single-gene network in conjunction with a simple negative interaction can also easily produce rhythms. We examine a model comprised of two well-differentiated parts. The first is a positive feedback created by a protein that binds to the promoter of its own gene and activates the transcription. The second is a negative interaction in which a repressor molecule prevents this protein from binding to its promoter. A stochastic study shows that the system is robust to noise. A deterministic study identifies that the dynamics of the oscillator are mainly driven by two types of biomolecules: the protein, and the complex formed by the repressor and this protein. The main conclusion of this paper is that a simple and usual negative interaction, such as degradation, sequestration or inhibition, acting on the positive transcriptional feedback of a single gene is a sufficient condition to produce reliable oscillations. One gene is enough and the positive transcriptional feedback signal does not need to activate a second repressor gene. This means that at the genetic level an explicit negative feedback loop is not necessary. The model needs neither cooperative binding reactions nor the formation of protein multimers. Therefore, our findings could help to clarify the design principles of cellular clocks and constitute a new efficient tool for engineering synthetic genetic oscillators.

References

[1]  Rust MJ, Markson JS, Lane WS, Fisher DS, O'Shea EK (2007) Ordered phosphorylation governs oscillation of a three-protein circadian clock. Science 318: 809–812.
[2]  O'Neill JS, Reddy AB (2011) Circadian clocks in human red blood cells. Nature 469: 498–503.
[3]  O'Neill JS, van Ooijen G, Dixon LE, Troein C, Corellou F, et al. (2011) Circadian rhythms persist without transcription in a eukaryote. Nature 469: 554–558.
[4]  Dunlap JC (1999) Molecular bases for circadian clocks. Cell 96: 271–290.
[5]  Young MW, Kay SA (2001) Time zones: a comparative genetics of circadian clocks. Nat Rev Genet 2: 702–715.
[6]  Elowitz MB, Leibler S (2000) A synthetic oscillatory network of transcriptional regulators. Nature 403: 335–338.
[7]  Atkinson MR, Savageau MA, Myers JT, Ninfa AJ (2003) Development of genetic circuitry exhibiting toggle switch or oscillatory behavior in Escherichia Coli. Cell 113: 597–607.
[8]  Fung E, Wong WW, Suen JK, Bulter T, Lee S, et al. (2005) A synthetic gene-metabolic oscillator. Nature 435: 118–122.
[9]  Stricker J, Cookson S, Bennett MR, Mather WH, Tsimring LS, et al. (2008) A fast, robust and tunable synthetic gene oscillator. Nature 456: 516–519.
[10]  Tigges M, Marquez-Lago TT, Stelling J, Fussenegger M (2009) A tunable synthetic mammalian oscillator. Nature 457: 309–312.
[11]  Toettcher JE, Mock C, Batchelor E, Loewer A, Lahav G (2010) A synthetic-natural hybrid oscillator in human cells. Proc Natl Acad Sci USA 107: 17047–17052.
[12]  Danino T, Mondragon-Palomino O, Tsimring L, Hasty J (2010) A synchronized quorum of genetic clocks. Nature 463: 326–330.
[13]  Goodwin BC (1965) Oscillatory behavior in enzymatic control processes. Adv Enzyme Regul 3: 425–438.
[14]  Goldbeter A (1995) A model for circadian oscillations in the Drosophila period protein (PER). Proc R Soc London Ser B 261: 319–324.
[15]  Ruoff P, Rensing L (1996) The temperature-compensated Goodwin model simulates many circadian clock properties. J Theor Biol 179: 275–285.
[16]  Leloup JC, Gonze D, Goldbeter A (1999) Limit cycle models for circadian rhythms based on transcriptional regulation in Drosophila and Neurospora. J Biol Rhythms 14: 433–448.
[17]  Ruoff P, Vinsjevik M, Monnerjahn C, Rensing L (2001) The Goodwin model: simulating the effect of light pulses on the circadian sporulation rhythm of Neurospora crassa. J Biol Rhythms 209: 29–42.
[18]  Gonze D, Halloy J, Goldbeter A (2002) Robustness of circadian rhythms with respect to molecular noise. Proc Natl Acad Sci USA 99: 673–678.
[19]  Bratsun D, Volfson D, Tsimring LS, Hasty J (2005) Delay-induced stochastic oscillations in gene regulation. Proc Natl Acad Sci USA 102: 14593–14598.
[20]  Griffith JS (1968) Mathematics of cellular control processes I. Negative feedback to one gene. J Theor Biol 20: 202–208.
[21]  Novák B, Tyson JJ (2008) Design principles of biochemical oscillators. Nat Rev Mol Cell Biol 9: 981–991.
[22]  Widder S, Schicho J, Schuster P (2007) Dynamic patterns of gene regulation I: Simple two-gene systems. J Theor Biol 246: 395–419.
[23]  Reppert SM, Weaver DR (2002) Coordination of circadian timing in mammals. Nature 418: 935–941.
[24]  Gallego M, Virshup DM (2007) Post-translationalmodifications regulate the ticking of the circadian clock. Nat Rev Mol Cell Biol 8: 139–148.
[25]  Purcell O, Savery NJ, Grierson CS, di Bernardo M (2010) A comparative analysis of synthetic genetic oscillators. J R Soc Interface 7: 1503–1524.
[26]  Barkai N, Leibler S (2000) Circadian clocks limited by noise. Nature 403: 267–268.
[27]  Smolen P, Baxter DA, Byrne JH (2001) Modeling circadian oscillations with interlocking positive and negative feedback loops. J Neurosci 21: 6644–6656.
[28]  Hasty J, Isaacs F, Dolnik M, McMillen D, Collins JJ (2001) Designer gene networks: Towards fundamental cellular control. Chaos 11: 207–220.
[29]  Leloup JC, Goldbeter A (2003) Toward a detailed computational model for the mammalian circadian clock. Proc Natl Acad Sci USA 100: 7051–7056.
[30]  Fran?ois P (2005) A model for the Neurospora circadian clock. Biophys J 88: 2369–2383.
[31]  Guantes R, Poyatos JF (2006) Dynamical principles of two-component genetic oscillators. PLoS Comput Biol 2: e30.
[32]  Hong CI, Jolma IW, Loros JJ, Dunlap JC, Ruoff P (2008) Simulating dark expressions and interactions of frq and wc-1 in the Neurospora circadian clock. Biophys J 94: 1221–1232.
[33]  Conrad E, Mayo AE, Ninfa AJ, Forger DB (2008) Rate constants rather than biochemical mechanism determine behaviour of genetic clocks. J R Soc Interface 5: S9–S15.
[34]  Munteanu A, Constante M, Isalan M, Sole R (2010) Avoiding transcription factor competition at promoter level increases the chances of obtaining oscillation. BMC Syst Biol 4: 66.
[35]  Becskei A, Seraphin B, Serrano L (2001) Positive feedback in eukaryotic gene networks: cell differentiation by graded to binary response conversion. EMBO J 20: 2528–2535.
[36]  Ferrell JE (2002) Self-perpetuating states in signal transduction: positive feedback, double-negative feedback and bistability. Curr Opin Cell Biol 14: 140–148.
[37]  Tsai TY, Choi YS, Ma W, Pomerening JR, Tang C, et al. (2008) Robust, tunable biological oscillations from interlinked positive and negative feedback loops. Science 321: 126–129.
[38]  Vilar JMG, Kueh HY, Barkai N, Leibler S (2002) Mechanisms of noise-resistance in genetic oscillators. Proc Natl Acad Sci USA 99: 5988–5992.
[39]  Mondragón-Palomino O, Danino T, Selimkhanov J, Tsimring L, Hasty J (2011) Entrainment of a population of synthetic genetic oscillators. Science 333: 1315–1319.
[40]  Griffith JS (1968) Mathematics of cellular control processes II. Positive feedback to one gene. J Theor Biol 20: 209–216.
[41]  Elowitz MB, Levine AJ, Siggia ED, Swain PS (2002) Stochastic gene expression in a single cell. Science 297: 1183–1186.
[42]  Swain PS, Elowitz MB, Siggia ED (2002) Intrinsic and extrinsic contributions to stochasticity in gene expression. Proc Natl Acad Sci USA 99: 12795–12800.
[43]  Murray JD (2002) Mathematical biology I: An introduction. New York: Springer. 551:
[44]  Strogatz SH (1994) Nonlinear dynamics and chaos: with applications to physics, biology, chemistry, and engineering. Addison-Wesley, Reading, MA. 498:
[45]  Tyson JJ, Chen KC, Novák B (2003) Sniffers, buzzers, toggles and blinkers: dynamics of regulatory and signaling pathways in the cell. Curr Opin Cell Biol 15: 221–231.
[46]  Gillespie DT (1977) Exact stochastic simulation of coupled chemical reactions. J Phys Chem 81: 2340–2361.
[47]  Dublanche Y, Michalodimitrakis K, Kümmerer N, Foglierini M, Serrano L (2006) Noise in transcription negative feedback loops: simulation and experimental analysis. Mol Syst Biol 2: 41.
[48]  Fall CP, Marland ES, Wagner JM, Tyson JJ (2002) Computational Cell Biology. Springer, Berlin. 468:
[49]  Buchler NE, Louis M (2008) Molecular titration and ultrasensitivity in regulatory networks. J Mol Biol 384: 1106–1119.
[50]  Buchler NE, Cross FR (2009) Protein sequestration generates a flexible ultrasensitive response in a genetic network. Mol Syst Biol 5: 272.

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133