Regulatory molecules present on the core promoter of a gene interact often in a dynamic,highly combinatorial and possibly energy-dependent manner, leading to complex promoter structure and even complex global dynamics...Regulatory molecules present on the core promoter of a gene interact often in a dynamic,highly combinatorial and possibly energy-dependent manner, leading to complex promoter structure and even complex global dynamics. The authors analyze dynamics of an arbitrarily complex promoter from the view of thermodynamics combined with statistic physics. First, the authors formulize transcription factors-mediated promoter kinetics in terms of energy. Then, the authors analyze energetic cost in several representative cases of promoter structure, deriving useful analytical results. Third, the authors derive analytical expressions for mean dwell times of the promoter activity states, experimentally measurable quantities related to the energy cost of promoter dynamics. The overall framework lays a theoretical foundation for analysis of complex promoter kinetics and gene expression dynamics.展开更多
Taking the famous genetic toggle switch as an example,we numerically investigated the effect of noise on bistability.We found that extrinsic noise resulting from stochastic fluctuations in synthesis and degradation ra...Taking the famous genetic toggle switch as an example,we numerically investigated the effect of noise on bistability.We found that extrinsic noise resulting from stochastic fluctuations in synthesis and degradation rates and from the environmental fluctuation in gene regulatory processes can induce coherent switch,and that there is an optimal noise intensity such that the noise not only can induce this switch,but also can amplify a weak input signal.In addition,we found that the intrinsic noise introduced through the Poisson τ-leap algorithm cannot induce such a switch.展开更多
A gene is often regulated by a variety of transcription factors, leading to complex promoter structure. However, how this structure affects gene expression remains elusive. Here, this paper studies a stochastic gene m...A gene is often regulated by a variety of transcription factors, leading to complex promoter structure. However, how this structure affects gene expression remains elusive. Here, this paper studies a stochastic gene model with the promoter containing arbitrarily many active and inactive states.First, the authors use the binomial moment method to derive analytical steady-state distributions of the mRNA and protein numbers. Then, the authors analytically investigate how the promoter structure impacts the mean expression levels and the expression noise. Third, numerical simulation finds interesting phenomena, e.g., the common on-off model overestimates the expression noise in contrast to multiple-state models; the multi-on mechanism can reduce the expression noise more than the multi-off mechanism if the mean expression level is kept the same; and multiple exits of transcription can result in multimodal distributions.展开更多
基金supported by Science and Technology Department under Grant No.2014CB964703the Natural Science Foundation under Grant Nos.91530320 and 11761025
文摘Regulatory molecules present on the core promoter of a gene interact often in a dynamic,highly combinatorial and possibly energy-dependent manner, leading to complex promoter structure and even complex global dynamics. The authors analyze dynamics of an arbitrarily complex promoter from the view of thermodynamics combined with statistic physics. First, the authors formulize transcription factors-mediated promoter kinetics in terms of energy. Then, the authors analyze energetic cost in several representative cases of promoter structure, deriving useful analytical results. Third, the authors derive analytical expressions for mean dwell times of the promoter activity states, experimentally measurable quantities related to the energy cost of promoter dynamics. The overall framework lays a theoretical foundation for analysis of complex promoter kinetics and gene expression dynamics.
基金the National Distinguished PhD Dissertations(200521)the National Natural Science Foundation of China(Grant No.60736208)
文摘Taking the famous genetic toggle switch as an example,we numerically investigated the effect of noise on bistability.We found that extrinsic noise resulting from stochastic fluctuations in synthesis and degradation rates and from the environmental fluctuation in gene regulatory processes can induce coherent switch,and that there is an optimal noise intensity such that the noise not only can induce this switch,but also can amplify a weak input signal.In addition,we found that the intrinsic noise introduced through the Poisson τ-leap algorithm cannot induce such a switch.
基金supported by Science and Technology Department under Grant No.2014CB964703the Natural Science Foundation under Grant Nos.91530320,11401448,61573011+1 种基金the Hubei Province Education Department under Grant No.B2016062the Science and Technology Department of Hubei Province under Grant Nos.2017CFB682 and 2018CFB688
文摘A gene is often regulated by a variety of transcription factors, leading to complex promoter structure. However, how this structure affects gene expression remains elusive. Here, this paper studies a stochastic gene model with the promoter containing arbitrarily many active and inactive states.First, the authors use the binomial moment method to derive analytical steady-state distributions of the mRNA and protein numbers. Then, the authors analytically investigate how the promoter structure impacts the mean expression levels and the expression noise. Third, numerical simulation finds interesting phenomena, e.g., the common on-off model overestimates the expression noise in contrast to multiple-state models; the multi-on mechanism can reduce the expression noise more than the multi-off mechanism if the mean expression level is kept the same; and multiple exits of transcription can result in multimodal distributions.
