Program in Systems Biology; Department of Microbiology and Physiological Systems; Graduate School of Biomedical Sciences
Amino Acids, Peptides, and Proteins | Bacteria | Systems and Integrative Physiology | Systems Biology
Transcription 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.
Systems Biology, Transcription factors, Escherichia coli
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DOI of Published Version
bioRxiv 2021.01.04.425191; doi: https://doi.org/10.1101/2021.01.04.425191. Link to preprint on bioRxiv.
Guharajan S, Chhabra S, Parisutham V, Brewster RC. (2021). Quantifying the regulatory role of individual transcription factors in Escherichia coli [preprint]. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1101/2021.01.04.425191. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1866
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