Negative Feedback Defining a Circadian Clock: Autoregulation of the Clock Gene
            <i>frequency</i>

Aronson, Benjamin D.; Johnson, Keith A.; Loros, Jennifer J.; Dunlap, Jay C.

doi:10.1126/science.8128244

Cited by 576 publications

(639 citation statements)

References 43 publications

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“…Genetic studies, initially carried out in the fruit fly Drosophila (Hardin et al 1990) and the fungus Neurospora (Aronson et al 1994), and later extended to mammals, showed that circadian oscillations are generated at the molecular level. The core molecular mechanism of these oscillations relies on the negative autoregulatory feedback exerted by clock proteins on the expression of their genes (Dunlap 1999;Young & Kay 2001).…”

Section: Introductionmentioning

confidence: 99%

Dependence of the period on the rate of protein degradation in minimal models for circadian oscillations

Gérard

Gonze

Goldbeter

2009

Phil. Trans. R. Soc. A.

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Circadian rhythms, which occur spontaneously with a period of about 24 h in a variety of organisms, allow their adaptation to the periodic variations of the environment. These rhythms are generated by a genetic regulatory network involving a negative feedback loop on transcription. Mathematical models based on the negative autoregulation of gene expression by the protein product of a clock gene account for the occurrence of selfsustained circadian oscillations. These models differ by their degree of complexity and, hence, by the number of variables considered. Some of these models can be considered as minimal because they contain a reduced number of biochemical processes and variables capable of producing sustained oscillations. In three of these minimal models, the period of the oscillations significantly changes with the rate of degradation of the clock protein. However, depending on the model considered, the period increases, decreases or passes through a maximum as a function of the protein degradation rate. We clarify the bases for these markedly different results by bringing to light the roles of (i) protein phosphorylation, which is required for protein degradation, and (ii) the velocity and degree of saturation of mRNA and protein degradation. Changes in the parameter values of the more complex of the minimal models can produce the period profiles observed in the other two models. The analysis allows us to reconcile the contradictory predictions for the dependence of the period on the clock protein degradation rate in three minimal models used to describe circadian rhythms.

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Section: Introductionmentioning

confidence: 99%

Dependence of the period on the rate of protein degradation in minimal models for circadian oscillations

Gérard

Gonze

Goldbeter

2009

Phil. Trans. R. Soc. A.

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“…In the dark, a heterodimeric WCC (D-WCC) binds to the C-box (the distal LRE) of the frq promoter, activating its transcription (Crosthwaite et al 1997;Cheng et al 2001b;Froehlich et al 2003;Dunlap and Loros 2004). On the other hand, FRQ and FRH (FRQinteraction RNA helicase), the negative elements in the loop, repress the transcription of frq by inhibiting WCC activity (Aronson et al 1994;Cheng et al 2001aCheng et al , 2005Denault et al 2001). The WC phosphorylation in the dark appears to be an important event in this process.…”

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confidence: 99%

Molecular mechanism of light responses in Neurospora: from light-induced transcription to photoadaptation

He¹,

Liu²

2005

Genes Dev.

193

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“…In Neurospora the circadian pacemaker is closely related to the expression of the frequency (frq) gene into its protein (FRQ), which is regulated by a negative feedback, i.e., expressed FRQ protein inhibits its own transcription [2,5]. In a 3-dimensional representation of the model (Fig.…”

Section: Local Curve Optimization For Temperature Compensationmentioning

confidence: 99%

Semi-algebraic optimization of temperature compensation in a general switch-type negative feedback model of circadian clocks

Aase

Ruoff

2007

J. Math. Biol.

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Temperature compensation is an essential property of circadian oscillators which enables them to act as physiological clocks. We have analyzed the temperature compensating behavior of a generalized transcriptional-translational negative feedback oscillator with a hard hysteretic switch and rate constants with an Arrheniustype temperature dependence. These oscillations can be considered as the result of a lowpass filtering operator acting on a train of rectangular pulses. Such a signalprocessing viewpoint makes it possible to express, in a semi-algebraic manner, the period length, the oscillator's control (sensitivity) coefficients, and the first and second-order derivatives of the period-temperature relationship. We have used the semi-algebraic approach to investigate a 3-dimensional Goodwin-type representation of the oscillator, where local optimization for temperature compensation has been considered. In the local optimization, activation energies are found, which lead to a zero first order derivative and to a closest-to-zero second order derivative at a given reference temperature. We find that the major contribution to temperature compensation over an extended temperature range is given by the (local) zero first order derivative, while only minor contributions to temperature compensation are given by an optimized second order derivative. In biological terms this could be interpreted to relate to a circadian clock mechanism which during evolution is being optimized for a certain but relative narrow (habitat) temperature range.

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Negative Feedback Defining a Circadian Clock: Autoregulation of the Clock Gene frequency

Cited by 576 publications

References 43 publications

Dependence of the period on the rate of protein degradation in minimal models for circadian oscillations

Dependence of the period on the rate of protein degradation in minimal models for circadian oscillations

Molecular mechanism of light responses in Neurospora: from light-induced transcription to photoadaptation

Semi-algebraic optimization of temperature compensation in a general switch-type negative feedback model of circadian clocks

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