Regulatory mechanisms set a gene's average level of expression, but a gene's 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 TF's nuclear concentration and the strength of its AD's 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.

Original languageEnglish
Article number111118
JournalCell Reports
Issue number3
StatePublished - Jul 19 2022


  • CP: Molecular biology
  • noise
  • single-cell variability
  • stochastic gene expression
  • synthetic biology
  • transcription
  • transcription factors
  • transcriptional regulation
  • yeast genetics


Dive into the research topics of 'Activation domains can decouple the mean and noise of gene expression'. Together they form a unique fingerprint.

Cite this