Feedback loops in the signal paths controlling gene expression

Šrobár, F.

doi:10.1016/j.bioelechem.2003.11.003

Cited by 2 publications

(4 citation statements)

References 11 publications

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“…(12). This is the well-known stabilizing effect of the negative feedback, in the absence of which, as in the case analyzed in [11], only sigmoidal versus 1 characteristics would be observed. The case of weakly bonded (K 2 = 0.6) repressor is presented in Fig.…”

Section: Results Of Numerical Evaluation and Discussionmentioning

confidence: 99%

“…Values of K 2 , the repressor constant of dissociation from RE, were varied. The rationale for choice of parameters values was discussed in [11]. Tightly bonded (K 2 = 0.2) repressor corresponds to monotonous versus 1 dependences, as shown in the upper panel of Fig.…”

Section: Results Of Numerical Evaluation and Discussionmentioning

confidence: 99%

“…Employing a symbolism simplified in comparison with that used in [13], let us denote, respectively, as 1 , 2 the activator and repressor concentrations, τ 1 and τ 2 their lifetimes (assuming first-order degradation kinetics), and as the low basal rate of activator synthesis in the absence of dimer. In studying the one-gene, one RE case [11], we worked with what we called the effective dimer concentration = 2 /( 2 + K ), where was the activator concentration and K the dissociation constant of its dimer from the RE. For small values, this quantity is proportional to square of the monomer concentration, reflecting straightforward kinetics of dimer formation.…”

Section: Gene Regulation System Encompassing Both Positive and Negatimentioning

confidence: 99%

“…Feeling that the notion of feedback in this context offers room for more elaboration, in [11] we used a special kind of diagrammatic representation [12] to assist the analysis of a simple gene regulation system encompassing one gene and one product protein -transcription factor (TF) binding as a dimer to the gene's responsive element (RE). In addition to forming a homodimer, the TF must be phosphorylated in order to act as transcriptional activator in the process of its own synthesis.…”

Section: Introductionmentioning

confidence: 99%

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Synergy of feedback mechanisms in gene regulation systems with promoter and repressor transcription factors

Šrobár

2008

Open Physics

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Abstract:Presence of feedback mechanisms, both positive and negative, in the gene regulation systems is generally appreciated. The present study proposes a diagrammatic representation of these phenomena that affords their exact formulation and reveals some new facts. Topology of feedback relationships is defined by diagram configuration and quantitative evaluation is afforded by analytical apparatus coming with the diagrams. In particular, criterion for occurrence of bistability and synergy of positive and negative feedback are described in exact manner using the concept of transmission functions associated with diagram edges. The approach is demonstrated on genetic regulatory system comprising two genes whose transcription is controlled by activator and repressor proteins mutually competing for binding to the same responsive element of the DNA.

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Section: Results Of Numerical Evaluation and Discussionmentioning

confidence: 99%

Section: Results Of Numerical Evaluation and Discussionmentioning

confidence: 99%

Section: Gene Regulation System Encompassing Both Positive and Negatimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Synergy of feedback mechanisms in gene regulation systems with promoter and repressor transcription factors

Šrobár

2008

Open Physics

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Modeling the Effects of Cell Cycle M-phase Transcriptional Inhibition on Circadian Oscillation

Kang

Chang

et al. 2008

PLoS Comput Biol

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Circadian clocks are endogenous time-keeping systems that temporally organize biological processes. Gating of cell cycle events by a circadian clock is a universal observation that is currently considered a mechanism serving to protect DNA from diurnal exposure to ultraviolet radiation or other mutagens. In this study, we put forward another possibility: that such gating helps to insulate the circadian clock from perturbations induced by transcriptional inhibition during the M phase of the cell cycle. We introduced a periodic pulse of transcriptional inhibition into a previously published mammalian circadian model and simulated the behavior of the modified model under both constant darkness and light–dark cycle conditions. The simulation results under constant darkness indicated that periodic transcriptional inhibition could entrain/lock the circadian clock just as a light–dark cycle does. At equilibrium states, a transcriptional inhibition pulse of certain periods was always locked close to certain circadian phases where inhibition on Per and Bmal1 mRNA synthesis was most balanced. In a light–dark cycle condition, inhibitions imposed at different parts of a circadian period induced different degrees of perturbation to the circadian clock. When imposed at the middle- or late-night phase, the transcriptional inhibition cycle induced the least perturbations to the circadian clock. The late-night time window of least perturbation overlapped with the experimentally observed time window, where mitosis is most frequent. This supports our hypothesis that the circadian clock gates the cell cycle M phase to certain circadian phases to minimize perturbations induced by the latter. This study reveals the hidden effects of the cell division cycle on the circadian clock and, together with the current picture of genome stability maintenance by circadian gating of cell cycle, provides a more comprehensive understanding of the phenomenon of circading gating of cell cycle.

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Feedback loops in the signal paths controlling gene expression

Cited by 2 publications

References 11 publications

Synergy of feedback mechanisms in gene regulation systems with promoter and repressor transcription factors

Synergy of feedback mechanisms in gene regulation systems with promoter and repressor transcription factors

Modeling the Effects of Cell Cycle M-phase Transcriptional Inhibition on Circadian Oscillation

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