Stochastic simulations of the repressilator circuit.

The genetic repressilator circuit consists of three transcription factors, or repressors, which negatively regulate each other in a cyclic manner. This circuit was synthetically constructed on plasmids in Escherichia coli and was found to exhibit oscillations in the concentrations of the three repressors. Since the repressors and their binding sites often appear in low copy numbers, the oscillations are noisy and irregular. Therefore, the repressilator circuit cannot be fully analyzed using deterministic methods such as rate equations. Here we perform stochastic analysis of the repressilator circuit using the master equation and Monte Carlo simulations. It is found that fluctuations modify the range of conditions in which oscillations appear as well as their amplitude and period, compared to the deterministic equations. The deterministic and stochastic approaches coincide only in the limit in which all the relevant components, including free proteins, plasmids, and bound proteins, appear in high copy numbers. We also find that subtle features such as cooperative binding and bound-repressor degradation strongly affect the existence and properties of the oscillations.