ArticleProceedings of the National Academy of Sciences of the United States of America2018
The calculation of transcript flux ratios reveals single regulatory mechanisms capable of activation and repression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25 citing papers in PubMed, 37 citations in OpenAlex.
- Serine/threonine protein kinase phosphorylation of DosR alters target gene transcription mechanics and regulates Mycobacterium tuberculosis response to nitric oxide stress.PLoS genetics · 2026Article
- Model-guided design of regulatable promoters for synthetic biology.Current opinion in microbiology · 2026Review
- Article
- A systematic survey of TF function in E. coli suggests RNAP stabilization is a prevalent strategy for both repressors and activators.Nucleic acids research · 2025Article
- Article
- House of CarDs: Functional insights into the transcriptional regulator CdnL.Molecular microbiology · 2024Review
- Macromolecular crowding has opposite effects on two critical sub-steps of transcription initiation.FEBS letters · 2024Article
- Regulation of the transcription factor CdnL promotes adaptation to nutrient stress inPNAS nexus · 2024Article
- Transcription factor interactions explain the context-dependent activity of CRX binding sites.PLoS computational biology · 2024Article
- High-throughput, fluorescent-aptamer-based measurements of steady-state transcription rates for the Mycobacterium tuberculosis RNA polymerase.Nucleic acids research · 2023Article
- High-throughput, fluorescent-aptamer-based measurements of steady-state transcription rates forbioRxiv : the preprint server for biology · 2023Article
- Diverse molecular mechanisms of transcription regulation by the bacterial alarmone ppGpp.Molecular microbiology · 2022Review
- Structural origins ofProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Rhodobacter sphaeroides CarD Negatively Regulates Its Own Promoter.Journal of bacteriology · 2021Article
- Bacterial transcription during growth arrest.Transcription · 2021Review
- Structural basis of transcriptional activation by the Mycobacterium tuberculosis intrinsic antibiotic-resistance transcription factor WhiB7.Molecular cell · 2021Article
- The Context-Dependent Influence of Promoter Sequence Motifs on Transcription Initiation Kinetics and Regulation.Journal of bacteriology · 2021Review
- A majority ofProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Rewiring of growth-dependent transcription regulation by a point mutation in region 1.1 of the housekeeping σ factor.Nucleic acids research · 2020Article
- Stepwise Promoter Melting by Bacterial RNA Polymerase.Molecular cell · 2020Article
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1 author at 1 institution in 1 country.
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Abstract
The regulation of transcription allows cells to adjust the rate of RNA polymerases (RNAPs) initiated in a promoter-specific manner. Classically, transcription factors are directed to a subset of promoters via the recognition of DNA sequence motifs. However, a unique class of regulators is recruited directly through interactions with RNAP. Surprisingly, these factors may still possess promoter specificity, and it has been postulated that the same kinetic mechanism leads to different regulatory outcomes depending on a promoter's basal rate constants. However, mechanistic studies of regulation typically report factor activity in terms of changes in the thermodynamics or kinetics of individual steps or states while qualitatively linking these observations to measured changes in transcript production. Here, I present online calculators that allow for the direct testing of mechanistic hypotheses by calculating the steady-state transcript flux in the presence and absence of a factor as a function of initiation rate constants. By evaluating how the flux ratio of a single kinetic mechanism varies across promoter space, quantitative insights into the potential of a mechanism to generate promoter-specific regulatory outcomes are obtained. Using these calculations, I predict that the mycobacterial transcription factor CarD is capable of repression in addition to its known role as an activator of ribosomal genes. In addition, a modification of the mechanism of the stringent response factors DksA/guanosine 5'-diphosphate 3'-diphosphate (ppGpp) is proposed based on their ability to differentially regulate transcription across promoter space. Overall, I conclude that a multifaceted kinetic mechanism is a requirement for differential regulation by this class of factors.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.