Anti-correlation of LacI association and dissociation rates observed in living cells
Abstract 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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56053-z |
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| _version_ | 1832594583605739520 |
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| author | Vinodh Kandavalli Spartak Zikrin Johan Elf Daniel Jones |
| author_facet | Vinodh Kandavalli Spartak Zikrin Johan Elf Daniel Jones |
| author_sort | Vinodh Kandavalli |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-de0cd0815771451ea42659f40db4762c |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-de0cd0815771451ea42659f40db4762c2025-01-19T12:31:16ZengNature PortfolioNature Communications2041-17232025-01-011611910.1038/s41467-025-56053-zAnti-correlation of LacI association and dissociation rates observed in living cellsVinodh Kandavalli0Spartak Zikrin1Johan Elf2Daniel Jones3Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala UniversityScience for Life Laboratory, Department of Cell and Molecular Biology, Uppsala UniversityScience for Life Laboratory, Department of Cell and Molecular Biology, Uppsala UniversityScience for Life Laboratory, Department of Cell and Molecular Biology, Uppsala UniversityAbstract 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.https://doi.org/10.1038/s41467-025-56053-z |
| spellingShingle | Vinodh Kandavalli Spartak Zikrin Johan Elf Daniel Jones Anti-correlation of LacI association and dissociation rates observed in living cells Nature Communications |
| title | Anti-correlation of LacI association and dissociation rates observed in living cells |
| title_full | Anti-correlation of LacI association and dissociation rates observed in living cells |
| title_fullStr | Anti-correlation of LacI association and dissociation rates observed in living cells |
| title_full_unstemmed | Anti-correlation of LacI association and dissociation rates observed in living cells |
| title_short | Anti-correlation of LacI association and dissociation rates observed in living cells |
| title_sort | anti correlation of laci association and dissociation rates observed in living cells |
| url | https://doi.org/10.1038/s41467-025-56053-z |
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