Analytical results for a non-Markovian process of gene expression with positive and negative feedbacks

Gene expression is a very complex process and involves many small biochemical reaction steps, resulting in a non-Markovian discrete stochastic process due to molecular memory between individual reactions. At present, this process is successfully investigated by generalized chemical master equation models. However, these models do not consider the role of feedback networks in gene expression. How the interaction between feedbacks and molecular memory affects gene expression still remains not well understood. Here, we establish generalized chemical master equation models of gene expression with positive and negative feedbacks. Assuming that the process of producing proteins follows an Erlang probability distribution, we obtain the analytical expression for this model in a steady state, as well as the measure of the noise of protein numbers. We further find that molecular memory competes with the positive feedback in suppressing the noise of the protein number. For our model with a negative feedback, molecular memory can strengthen the intensity of suppressing this noise. These interesting results imply that molecular memory are as important as the feedbacks to affect gene expression.