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dc.contributor.authorGuharajan, Sunil
dc.contributor.authorChhabra, Shivani
dc.contributor.authorParisutham, Vinuselvi
dc.contributor.authorBrewster, Robert C
dc.date2022-08-11T08:08:26.000
dc.date.accessioned2022-08-23T15:54:57Z
dc.date.available2022-08-23T15:54:57Z
dc.date.issued2021-01-04
dc.date.submitted2021-01-20
dc.identifier.citation<p>bioRxiv 2021.01.04.425191; doi: https://doi.org/10.1101/2021.01.04.425191. <a href="https://doi.org/10.1101/2021.01.04.425191" target="_blank" title="preprint on bioRxiv">Link to preprint on bioRxiv.</a></p>
dc.identifier.doi10.1101/2021.01.04.425191
dc.identifier.urihttp://hdl.handle.net/20.500.14038/29650
dc.description.abstractTranscription factors (TFs) modulate gene expression by binding to regulatory DNA sequences surrounding target genes. To isolate the fundamental regulatory interactions of E. coli TFs, we measure regulation of TFs acting on synthetic target genes that are designed to isolate the individual TF regulatory effect. This data is interpreted through a thermodynamic model that decouples the role of TF copy number and TF binding affinity from the interactions of the TF on RNA polymerase through two distinct mechanisms: (de)stabilization of the polymerase and (de)acceleration of transcription initiation. We find the contribution of each mechanism towards the observed regulation depends on TF identity and binding location; for the set of TFs studied here, regulation immediately downstream of the promoter is not sensitive to TF identity, however these same TFs regulate through distinct mechanisms at an upstream binding site. Furthermore, depending on binding location, these two mechanisms of regulation can act coherently, to reinforce the observed regulatory role (activation or repression), or incoherently, where the TF regulates two distinct steps with opposing effect.
dc.language.isoen_US
dc.relationNow published in Cell Reports doi: 10.1016/j.celrep.2021.109952
dc.rightsThe 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 4.0 International license.
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.subjectSystems Biology
dc.subjectTranscription factors
dc.subjectEscherichia coli
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectBacteria
dc.subjectSystems and Integrative Physiology
dc.titleQuantifying the regulatory role of individual transcription factors in Escherichia coli [preprint]
dc.typePreprint
dc.source.journaltitlebioRxiv
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2897&amp;context=faculty_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/1866
dc.identifier.contextkey21185977
refterms.dateFOA2022-08-23T15:54:57Z
html.description.abstract<p><p id="x-x-x-x-p-2">Transcription factors (TFs) modulate gene expression by binding to regulatory DNA sequences surrounding target genes. To isolate the fundamental regulatory interactions of <em>E. coli</em> TFs, we measure regulation of TFs acting on synthetic target genes that are designed to isolate the individual TF regulatory effect. This data is interpreted through a thermodynamic model that decouples the role of TF copy number and TF binding affinity from the interactions of the TF on RNA polymerase through two distinct mechanisms: (de)stabilization of the polymerase and (de)acceleration of transcription initiation. We find the contribution of each mechanism towards the observed regulation depends on TF identity and binding location; for the set of TFs studied here, regulation immediately downstream of the promoter is not sensitive to TF identity, however these same TFs regulate through distinct mechanisms at an upstream binding site. Furthermore, depending on binding location, these two mechanisms of regulation can act coherently, to reinforce the observed regulatory role (activation or repression), or incoherently, where the TF regulates two distinct steps with opposing effect.</p>
dc.identifier.submissionpathfaculty_pubs/1866
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.contributor.departmentDepartment of Microbiology and Physiological Systems
dc.contributor.departmentProgram in Systems Biology


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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 4.0 International license.
Except where otherwise noted, this item's license is described as 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 4.0 International license.