UC Berkeley

Regulatory mechanisms set a genes average level of expression, but a genes expression constantly fluctuates around that average. These stochastic fluctuations, or expression noise, play a role in cell-fate transitions, bet hedging in microbes, and the development of chemotherapeutic resistance in cancer. An outstanding question is what regulatory mechanisms contribute to noise. Here, we demonstrate that, for a fixed mean level of expression, strong activation domains (ADs) at low abundance produce high expression noise, while weak ADs at high abundance generate lower expression noise. We conclude that differences in noise can be explained by the interplay between a TFs nuclear concentration and the strength of its ADs effect on mean expression, without invoking differences between classes of ADs. These results raise the possibility of engineering gene expression noise independently of mean levels in synthetic biology contexts and provide a potential mechanism for natural selection to tune the noisiness of gene expression.