Exact results for queuing models of stochastic transcription with memory and crosstalk

Gene transcription is a complex multistep biochemical process, which can create memory between individual reaction events. On the other hand, many inducible genes, when activated by external cues, are often coregulated by several competitive pathways with crosstalk. This raises an unexplored question: how do molecular memory and crosstalk together affect gene expressions? To address this question, we introduce a queuing model of stochastic transcription, where two crossing signaling pathways are used to direct gene activation in response to external signals and memory functions to model multistep reaction processes involved in transcription. We first establish, based on the total probability principle, the chemical master equation for this queuing model, and then we derive, based on the binomial moment approach, exact expressions for statistical quantities (including distributions) of mRNA, which provide insights into the roles of crosstalk and memory in controlling the mRNA level and noise. We find that molecular memory of gene activation decreases the mRNA level but increases the mRNA noise, and double activation pathways always reduce the mRNA noise in contrast to a single pathway. In addition, we find that molecular memory can make the mRNA bimodality disappear.