ArticlePLoS computational biology2011
Speed, sensitivity, and bistability in auto-activating signaling circuits.
Article in PLoS computational biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- Continuous negative autoregulation fine-tunes dosage-sensitive transcription factor expression to maintain post-mitotic neuron identity.bioRxiv : the preprint server for biology · 2026Article
- The Dynamics of Inducible Genetic Circuits.ArXiv · 2026Article
- The Interplay Between Non-Instantaneous Dynamics of mRNA and Bounded Extrinsic Stochastic Perturbations for a Self-Enhancing Transcription Factor.Entropy (Basel, Switzerland) · 2026Article
- Model-guided gene circuit design for engineering genetically stable cell populations in diverse applications.Journal of the Royal Society, Interface · 2025Article
- The two-component system TtrRS boosts Vibrio parahaemolyticus colonization by exploiting sulfur compounds in host gut.PLoS pathogens · 2024Article
- A coarse-grained bacterial cell model for resource-aware analysis and design of synthetic gene circuits.Nature communications · 2024Article
- Theoretical and computational tools to model multistable gene regulatory networks.Reports on progress in physics. Physical Society (Great Britain) · 2023Review
- Sequestration of histidine kinases by non-cognate response regulators establishes a threshold level of stimulation for bacterial two-component signaling.Nature communications · 2023Article
- Exploring the mono-/bistability range of positively autoregulated signaling systems in the presence of competing transcription factor binding sites.PLoS computational biology · 2022Article
- Controlling gene expression timing through gene regulatory architecture.PLoS computational biology · 2022Article
- Regulator-dependent temporal dynamics of a restriction-modification system's gene expression upon entering new host cells: single-cell and population studies.Nucleic acids research · 2021Article
- Role of a local transcription factor in governing cellular carbon/nitrogen homeostasis in Pseudomonas fluorescens.Nucleic acids research · 2021Article
- Overlaid positive and negative feedback loops shape dynamical properties of PhoPQ two-component system.PLoS computational biology · 2021Article
- Application of combinatorial optimization strategies in synthetic biology.Nature communications · 2020Review
- Stochastic Modeling of Autoregulatory Genetic Feedback Loops: A Review and Comparative Study.Biophysical journal · 2020Review
- Revisiting the Reduction of Stochastic Models of Genetic Feedback Loops with Fast Promoter Switching.Biophysical journal · 2019Article
- Identification of an Autorepressing Two-Component Signaling System That Modulates Virulence in Streptococcus suis Serotype 2.Infection and immunity · 2019Article
- Added value of autoregulation and multi-step kinetics of transcription initiation.Royal Society open science · 2018Article
- Overcoming the Cost of Positive Autoregulation by Accelerating the Response with a Coupled Negative Feedback.Cell reports · 2018Article
- Assigning function to natural allelic variation via dynamic modeling of gene network induction.Molecular systems biology · 2018Article
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Authors and funding
3 authors.
Funding
Abstract
Cells employ a myriad of signaling circuits to detect environmental signals and drive specific gene expression responses. A common motif in these circuits is inducible auto-activation: a transcription factor that activates its own transcription upon activation by a ligand or by post-transcriptional modification. Examples range from the two-component signaling systems in bacteria and plants to the genetic circuits of animal viruses such as HIV. We here present a theoretical study of such circuits, based on analytical calculations, numerical computations, and simulation. Our results reveal several surprising characteristics. They show that auto-activation can drastically enhance the sensitivity of the circuit's response to input signals: even without molecular cooperativity, an ultra-sensitive threshold response can be obtained. However, the increased sensitivity comes at a cost: auto-activation tends to severely slow down the speed of induction, a stochastic effect that was strongly underestimated by earlier deterministic models. This slow-induction effect again requires no molecular cooperativity and is intimately related to the bimodality recently observed in non-cooperative auto-activation circuits. These phenomena pose strong constraints on the use of auto-activation in signaling networks. To achieve both a high sensitivity and a rapid induction, an inducible auto-activation circuit is predicted to acquire low cooperativity and low fold-induction. Examples from Escherichia coli's two-component signaling systems support these predictions.
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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.