Transcriptional control of noise in gene expression

Cis-regulatory control of transcription is the dominant form of regulation of gene expression. Recent experimental results suggest that, in addition to the mean expression level, cell-to-cell variability might also be transcriptionally regulated. Here, we develop a stochastic model of transcriptional regulation that allows us to calculate closed-form analytical expressions for the mean and variance of the protein and mRNA distributions for an arbitrarily complex cis-regulatory motif. Our model allows us to investigate how noise may be transcriptionally regulated independently from the mean expression. We show that our approach is in excellent agreement with stochastic simulations and experiment, and leads to an experimentally testable formula for the noise in gene expression as a function of inducer-molecule concentrations.