Distributions for negative-feedback-regulated stochastic gene expression: dimension reduction and numerical solution of the chemical master equation.
In this work we introduce a novel approach to study biochemical noise. It comprises a simplification of the master equation of complex reaction schemes (via an adiabatic approximation) and the numerical solution of the reduced master equation. The accuracy of this procedure is tested by comparing its results with analytic solutions (when available) and with Gillespie stochastic simulations. We further employ our approach to study the stochastic expression of a simple gene network, which is subject to negative feedback regulation at the transcriptional level. Special attention is paid to the influence of negative feedback on the amplitude of intrinsic noise, as well as on the relaxation rate of the system probability distribution function to the steady solution. Our results suggest the existence of an optimal feedback strength that maximizes this relaxation rate.
Departamento de Matemáticas, Centro de Investigación y de Estudios Avanzados del IPN, Av Instituto Politécnico Nacional 2508, 07360 México DF, Mexico.
Eduardo S
ES
Zeron
Moisés
M
Santillán
D000465:Algorithms; D025461:Feedback, Physiological; D005786:Gene Expression Regulation / Q000235:genetics*; D053263:Gene Regulatory Networks; D008957:Models, Genetic; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D013269:Stochastic Processes
D011506:Proteins; D012333:RNA, Messenger