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Promoter sequence determines the relationship between expression level and noise. (2013)

Carey, L.B., van Dijk, D., Sloot, P.M., Kaandorp, J.A., Segal, E.

In response to environmental changes, cells regulate the activity of transcription factors (TFs), which in turn change the expression of dozens of downstream target genes by binding to their promoters. The response of each target gene is determined by the interplay between TF concen- tration and the context in which TF binding sites occur in each target promoter. To examine the relationship between promoter sequence, mechanism of regulation, and response to TF activity, we measured expression of 16 target genes of a single TF in response to changes in TF concentration in single cells. We found that different native promoters that are all targets of the same TF exhibit diverse responses to changing TF levels in terms of both gene expression level and cell-to-cell variability (noise) in expression. Using computational modeling and mutations of specific promoter elements, we show that the molecular mechanisms of regulation can be inferred by measuring how noise changes with expression. These results show that a single TF can regulate transcription through multiple mechanisms, resulting in similar changes in mean expression but vastly different changes in cell-to-cell variability.

PLoS Biology 11: e1001528. doi: 10.1371/journal.pbio.1001528

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