Stochastic Gene Expression under Sequestration: Noise Reduction and Emergent Distributions

Gene expression noise can be modulated by protein sequestration, a mechanism we investigate through a stochastic modeling framework. We examine how the distribution of free (non-sequestered) protein depends on sequestration cooperativity (monomers, dimers, multimers) and on the timescale separation between sequestration and protein turnover. For non-cooperative sequestration, faster kinetics drive the distribution from a high-noise to a lower-noise gamma form, while the right-tail remains governed by the high-noise limit — revealing a non-commutativity between tail asymptotics and fast sequestration. For cooperative sequestration, the distribution departs from gamma, exhibiting left skewness or multi-modality. These results highlight how sequestration mechanisms shape protein variability in nontrivial ways.