A common repressor pool results in indeterminacy of extrinsic noise

For just over a decade, stochastic gene expression has been the focus of many experimental and theoretical studies. It is now widely accepted that noise in gene expression can be decomposed into extrinsic and intrinsic components, which have orthogonal contributions to the total noise. Intrinsic noise stems from the random occurrence of biochemical reactions and is inherent to gene expression. Extrinsic noise originates from fluctuations in the concentrations of regulatory components or random transitions in the cell's state and is imposed to the gene of interest by the intra- and extra-cellular environment. The basic assumption has been that extrinsic noise acts as a pure input on the gene of interest, which exerts no feedback on the extrinsic noise source. Thus, multiple copies of a gene would be uniformly influenced by an extrinsic noise source. Here, we report that this assumption falls short when multiple genes share a common pool of a regulatory molecule. Due to the competitive utilization of the molecules existing in this pool, genes are no longer uniformly influenced by the extrinsic noise source. Rather, they exert negative regulation on each other and thus extrinsic noise cannot be determined by the currently established method.