Dataset Information

Guisoni2016 - Cis-regulatory system (CRS) can drive sustained oscillations

ABSTRACT: Guisoni2016 - Cis-regulatory system (CRS) can drive sustained oscillations This model is described in the article: Promoters Architecture-Based Mechanism for Noise-Induced Oscillations in a Single-Gene Circuit. Guisoni N, Monteoliva D, Diambra L. PLoS ONE 2016; 11(3): e0151086 Abstract: It is well known that single-gene circuits with negative feedback loop can lead to oscillatory gene expression when they operate with time delay. In order to generate these oscillations many processes can contribute to properly timing such delay. Here we show that the time delay coming from the transitions between internal states of the cis-regulatory system (CRS) can drive sustained oscillations in an auto-repressive single-gene circuit operating in a small volume like a cell. We found that the cooperative binding of repressor molecules is not mandatory for a oscillatory behavior if there are enough binding sites in the CRS. These oscillations depend on an adequate balance between the CRS kinetic, and the synthesis/degradation rates of repressor molecules. This finding suggest that the multi-site CRS architecture can play a key role for oscillatory behavior of gene expression. Finally, our results can also help to synthetic biologists on the design of the promoters architecture for new genetic oscillatory circuits. This model is hosted on BioModels Database and identified by: MODEL1611030000. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

SUBMITTER: Luis Diambra

PROVIDER: MODEL1611030000 | BioModels | 2016-11-03

REPOSITORIES: BioModels

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Publications

Promoters Architecture-Based Mechanism for Noise-Induced Oscillations in a Single-Gene Circuit.

Guisoni N N Monteoliva D D Diambra L L

PloS one 20160309 3

It is well known that single-gene circuits with negative feedback loop can lead to oscillatory gene expression when they operate with time delay. In order to generate these oscillations many processes can contribute to properly timing such delay. Here we show that the time delay coming from the transitions between internal states of the cis-regulatory system (CRS) can drive sustained oscillations in an auto-repressive single-gene circuit operating in a small volume like a cell. We found that the ...[more]

PMID: 26958852

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Project description:Karapetyan2016 - Genetic oscillatory network - Repressor Titration Circuit (RTC) This model is described in the article: Role of DNA binding sites and slow unbinding kinetics in titration-based oscillators. Karapetyan S, Buchler NE. Phys Rev E Stat Nonlin Soft Matter Phys 2015 Dec; 92(6-1): 062712 Abstract: Genetic oscillators, such as circadian clocks, are constantly perturbed by molecular noise arising from the small number of molecules involved in gene regulation. One of the strongest sources of stochasticity is the binary noise that arises from the binding of a regulatory protein to a promoter in the chromosomal DNA. In this study, we focus on two minimal oscillators based on activator titration and repressor titration to understand the key parameters that are important for oscillations and for overcoming binary noise. We show that the rate of unbinding from the DNA, despite traditionally being considered a fast parameter, needs to be slow to broaden the space of oscillatory solutions. The addition of multiple, independent DNA binding sites further expands the oscillatory parameter space for the repressor-titration oscillator and lengthens the period of both oscillators. This effect is a combination of increased effective delay of the unbinding kinetics due to multiple binding sites and increased promoter ultrasensitivity that is specific for repression. We then use stochastic simulation to show that multiple binding sites increase the coherence of oscillations by mitigating the binary noise. Slow values of DNA unbinding rate are also effective in alleviating molecular noise due to the increased distance from the bifurcation point. Our work demonstrates how the number of DNA binding sites and slow unbinding kinetics, which are often omitted in biophysical models of gene circuits, can have a significant impact on the temporal and stochastic dynamics of genetic oscillators. This model is hosted on BioModels Database and identified by: BIOMD0000000587. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Project description:Karapetyan2016 - Genetic oscillatory network - Activator Titration Circuit (ATC) This model is described in the article: Role of DNA binding sites and slow unbinding kinetics in titration-based oscillators. Karapetyan S, Buchler NE. Phys Rev E Stat Nonlin Soft Matter Phys 2015 Dec; 92(6-1): 062712 Abstract: Genetic oscillators, such as circadian clocks, are constantly perturbed by molecular noise arising from the small number of molecules involved in gene regulation. One of the strongest sources of stochasticity is the binary noise that arises from the binding of a regulatory protein to a promoter in the chromosomal DNA. In this study, we focus on two minimal oscillators based on activator titration and repressor titration to understand the key parameters that are important for oscillations and for overcoming binary noise. We show that the rate of unbinding from the DNA, despite traditionally being considered a fast parameter, needs to be slow to broaden the space of oscillatory solutions. The addition of multiple, independent DNA binding sites further expands the oscillatory parameter space for the repressor-titration oscillator and lengthens the period of both oscillators. This effect is a combination of increased effective delay of the unbinding kinetics due to multiple binding sites and increased promoter ultrasensitivity that is specific for repression. We then use stochastic simulation to show that multiple binding sites increase the coherence of oscillations by mitigating the binary noise. Slow values of DNA unbinding rate are also effective in alleviating molecular noise due to the increased distance from the bifurcation point. Our work demonstrates how the number of DNA binding sites and slow unbinding kinetics, which are often omitted in biophysical models of gene circuits, can have a significant impact on the temporal and stochastic dynamics of genetic oscillators. This model is hosted on BioModels Database and identified by: BIOMD0000000586. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

Guisoni2016 - Cis-regulatory system (CRS) can drive sustained oscillations

Publications

Promoters Architecture-Based Mechanism for Noise-Induced Oscillations in a Single-Gene Circuit.

Similar Datasets

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