Small protein number effects in stochastic models of autoregulated bursty gene expression

A stochastic model of autoregulated bursty gene expression by Kumar et al. [Phys. Rev. Lett. 113, 268105 (2014)] has been exactly solved in steady-state conditions under the implicit assumption that protein numbers are sufficiently large such that fluctuations in protein numbers due to reversible protein-promoter binding can be ignored. Here, we derive an alternative model that takes into account these fluctuations and, hence, can be used to study low protein number effects. The exact steady-state protein number distribution is derived as a sum of Gaussian hypergeometric functions. We use the theory to study how promoter switching rates and the type of feedback influence the size of protein noise and noise-induced bistability. Furthermore, we show that our model predictions for the protein number distribution are significantly different from those of Kumar et al. when the protein mean is small, gene switching is fast, and protein binding to the gene is faster than the reverse unbinding reaction.