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Anti-correlation of LacI association and dissociation rates observed in living cells
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Anti-correlation of LacI association and dissociation rates observed in living cells
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Journal Article
Anti-correlation of LacI association and dissociation rates observed in living cells
2025
Overview
The rate at which transcription factors (TFs) bind their cognate sites has long been assumed to be limited by diffusion, and thus independent of binding site sequence. Here, we systematically test this assumption using cell-to-cell variability in gene expression as a window into the in vivo association and dissociation kinetics of the model transcription factor LacI. Using a stochastic model of the relationship between gene expression variability and binding kinetics, we performed single-cell gene expression measurements to infer association and dissociation rates for a set of 35 different LacI binding sites. We found that both association and dissociation rates differed significantly between binding sites, and moreover observed a clear anticorrelation between these rates across varying binding site strengths. These results contradict the long-standing hypothesis that TF binding site strength is primarily dictated by the dissociation rate, but may confer the evolutionary advantage that TFs do not get stuck in near-operator sequences while searching.
What makes a transcription factor (TF) binding site “strong”: slow TF dissociation, or fast TF association? Kandavalli et al found that stronger sites had both slower dissociation and faster association compared to weaker sites in vivo.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
