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Competition between binding sites determines gene expression at low transcription factor concentrations

David van Dijk, View ORCID ProfileEilon Sharon, View ORCID ProfileMaya Lotan-Pompan, View ORCID ProfileAdina Weinberger, View ORCID ProfileLucas B. Carey, View ORCID ProfileEran Segal
doi: https://doi.org/10.1101/033753
David van Dijk
1Department of Biological Sciences, Department of Systems Biology, Columbia University, New York, NY, USA
2Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel
3Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
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Eilon Sharon
5Current address: Department of Genetics, Stanford University, Stanford, California, United States of America
2Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel
3Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
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Maya Lotan-Pompan
2Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel
3Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
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Adina Weinberger
2Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel
3Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
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Lucas B. Carey
4Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Dr. Aiguader 88, 08003 Barcelona, Spain.
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  • For correspondence: eran.segal@weizmann.ac.il lucas.carey@upf.edu
Eran Segal
2Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel
3Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
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  • For correspondence: eran.segal@weizmann.ac.il lucas.carey@upf.edu
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Abstract

The response of gene expression to intra- and extra-cellular cues is largely mediated through changes in the activity of transcription factors (TFs), whose sequence specificities are largely known. However, the rules by which promoters decode the amount of active TF into gene expression are not well understood. Here, we measure the activity of 6500 designed promoters at six different levels of TF activity in budding yeast. We observe that maximum promoter activity is determined by TF activity and not by the number of sites. Surprisingly, the addition of an activator-binding site often reduces expression. A thermodynamic model that incorporates competition between neighboring binding sites for a local pool of TF molecules explains this behavior and accurately predicts both absolute expression and the amount by which addition of a site increases or reduces expression. Taken together, our findings support a model in which neighboring binding sites interact competitively when TF is limiting but otherwise act additively.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted December 17, 2015.
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Competition between binding sites determines gene expression at low transcription factor concentrations
David van Dijk, Eilon Sharon, Maya Lotan-Pompan, Adina Weinberger, Lucas B. Carey, Eran Segal
bioRxiv 033753; doi: https://doi.org/10.1101/033753
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Competition between binding sites determines gene expression at low transcription factor concentrations
David van Dijk, Eilon Sharon, Maya Lotan-Pompan, Adina Weinberger, Lucas B. Carey, Eran Segal
bioRxiv 033753; doi: https://doi.org/10.1101/033753

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