Variability of the distribution of differentiation pathway choices regulated by a multipotent delayed stochastic switch

Ribeiro, André S.; Dai, Xiaofeng; Yli‐Harja, Olli

doi:10.1016/j.jtbi.2009.05.025

Cited by 8 publications

(4 citation statements)

References 40 publications

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“…For a wide range of parameter values, the delayed stochastic switch has two noisy attractors [7,35]. We assess the stability from the number of switches between the noisy attractors in the time series.…”

Section: Reactions Of Interactions Between Repressors and Promoters Amentioning

confidence: 99%

Dynamics of a genetic toggle switch at the nucleotide and codon levels

et al. 2011

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We study the dynamics of a model stochastic two-gene switch at the nucleotide and codon levels. First, we show that its stability, the mean lifetime of the noisy attractors, differs from that of a model where transcription and translation elongation are modeled as single-step delayed events, indicating the need of detailed models to study the dynamics of switches. Next, we vary the coupling between the two genes by varying the affinity of repressor proteins to the promoters and measure the mutual information between the two proteins times series. We find that there is a degree of coupling that maximizes information propagation between the two genes. This is explained by the effects of the coupling on mean and entropy of RNA and protein numbers of each gene, as well as correlation, 2-tuple entropy between the two proteins numbers, and, finally, the stability of the noisy attractors. We also find that increasing the rate of translation initiation increases the correlation between RNA and protein numbers and between the two proteins, due to increased stability of the noisy attractors. Increasing the rate of transcription or decreasing RNA degradation causes opposite effects to the correlation between RNA and proteins of each gene and the stability of the noisy attractors. Finally, we add a sequence-dependent transcription pause site and show that both its probability of occurrence, as well as its mean time length, affects the dynamics of the switch, further demonstrating the dependence of the dynamics of this circuit on sequence level events.

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Section: Reactions Of Interactions Between Repressors and Promoters Amentioning

confidence: 99%

Dynamics of a genetic toggle switch at the nucleotide and codon levels

et al. 2011

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“…One consequence of multiscale modelling is the need to have a detailed but simple description of the intracellular dynamics, with mechanisms to create heterogeneity between cells. Stochastic processes are compatible with the multiscale framework developed here and have been well studied in the context of intracellular networks [22,27,19,28,33]. In a recent review, Byrne and Drasdo discussed the merits of individual-based models and continuum models of cell populations [7].…”

Section: Discussionmentioning

confidence: 88%

How to Build a Multiscale Model in Biology

Bernard

2013

Acta Biotheor

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Biological processes span several scales in space, from the single molecules to organisms and ecosystems. Multiscale modelling approaches in biology are useful to take into account the complex interactions between different organisation levels in those systems. We review several single- and multiscale models, from the most simple to the complex ones, and discuss their properties from a multiscale point of view. Approaches based on master equations for stochastic processes, individual-based models, hybrid continuous-discrete models and structured PDE models are presented.

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“…Our simplified model of pathway choice of cell differentiation assumes that the two dimers expressed by the TS are also transcription factors of another gene (or genes), responsible for determining the differentiation pathway [40]. We assume two cases, one where non-functional dimers affect the differentiation pathway choice, and one where they do not.…”

Section: Cell Differentiation Mechanismmentioning

confidence: 99%

Tuning cell differentiation patterns and single cell dynamics by regulating proteins’ functionalities in a toggle switch

Dai¹,

Healy²,

Yli‐Harja³

et al. 2009

Journal of Theoretical Biology

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We investigate how the regulation of protein multi-functionalities affect the dynamics of a stochastic model of a toggle switch and the differentiation pattern of cell population regulated by the switch. We study the effects of loss of functionality in DNA-binding and repression and the involvement in differentiation pathway choice. First is shown how the patterns of cell differentiation differ, when each of these functionalities is fully non-functional. Next, tuning the fraction of non-functional proteins regarding the ability to bind DNA is shown to allow fine tuning of the switch and cell differentiation pattern dynamics. Finally, biasing the probability of functionality of the two proteins biases the dynamics of the switch and cell differentiation patterns, especially when transcription factors retain the ability to bind DNA but have lost the ability to repress gene expression. Our results suggest that, besides transcriptional and translational levels of regulation, activation of functionalities in multi-functional proteins are an important regulator of gene networks.

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Variability of the distribution of differentiation pathway choices regulated by a multipotent delayed stochastic switch

Cited by 8 publications

References 40 publications

Dynamics of a genetic toggle switch at the nucleotide and codon levels

Dynamics of a genetic toggle switch at the nucleotide and codon levels

How to Build a Multiscale Model in Biology

Tuning cell differentiation patterns and single cell dynamics by regulating proteins’ functionalities in a toggle switch

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