ArticleProceedings of the National Academy of Sciences of the United States of America2024
Flexibility and sensitivity in gene regulation out of equilibrium.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22 citing papers in PubMed.
- The Trajectory Statistics of Biological Exploratory Dynamics.bioRxiv : the preprint server for biology · 2026Article
- Stable epigenetic states set single-cell activation thresholds in mammalian expression systems.bioRxiv : the preprint server for biology · 2026Article
- Invariant nonequilibrium dynamics in gene regulation optimize information flow.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Decoupling between activation time and steady-state level in input-output responses.PLoS computational biology · 2026Article
- Mechanisms of enhanced or impaired DNA target selectivity driven by protein dimerization.PNAS nexus · 2026Article
- Bifunctional transcriptional effector domains control gene expression pulses in an occupancy-dependent manner.bioRxiv : the preprint server for biology · 2025Article
- Widespread low-affinity motifs enhance chromatin accessibility and regulatory potential in mESCs.bioRxiv : the preprint server for biology · 2025Article
- Article
- Identification and understanding of allostery hotspots in proteins: Integration of deep mutational scanning and multi-faceted computational analyses.Journal of molecular biology · 2025Review
- Emergence of activation or repression in transcriptional control under a fixed molecular context.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Decoupling between activation time and steady-state level in input-output responses.bioRxiv : the preprint server for biology · 2025Article
- Limits on the computational expressivity of non-equilibrium biophysical processes.Nature communications · 2025Article
- Mechanisms of enhanced or impaired DNA target selectivity driven by protein dimerization.bioRxiv : the preprint server for biology · 2025Article
- Ecosystems as adaptive living circuits.bioRxiv : the preprint server for biology · 2025Article
- Stochastic thermodynamics for biological functions.Quantitative biology (Beijing, China) · 2025Review
- Deciphering regulatory architectures of bacterial promoters from synthetic expression patterns.PLoS computational biology · 2024Article
- Article
- Deciphering regulatory architectures from synthetic single-cell expression patterns.bioRxiv : the preprint server for biology · 2024Article
- The Hill function is the universal Hopfield barrier for sharpness of input-output responses.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Governing principles of transcriptional logic out of equilibrium.Biophysical journal · 2024Article
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5 authors.
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Abstract
Cells adapt to environments and tune gene expression by controlling the concentrations of proteins and their kinetics in regulatory networks. In both eukaryotes and prokaryotes, experiments and theory increasingly attest that these networks can and do consume biochemical energy. How does this dissipation enable cellular behaviors forbidden in equilibrium? This open question demands quantitative models that transcend thermodynamic equilibrium. Here, we study the control of simple, ubiquitous gene regulatory networks to explore the consequences of departing equilibrium in transcription. Employing graph theory to model a set of especially common regulatory motifs, we find that dissipation unlocks nonmonotonicity and enhanced sensitivity of gene expression with respect to a transcription factor's concentration. These features allow a single transcription factor to act as both a repressor and activator at different concentrations or achieve outputs with multiple concentration regimes of locally enhanced sensitivity. We systematically dissect how energetically driving individual transitions within regulatory networks, or pairs of transitions, generates a wide range of more adjustable and sensitive phenotypic responses than in equilibrium. These results generalize to more complex regulatory scenarios, including combinatorial control by multiple transcription factors, which we relate and often find collapse to simple mathematical behaviors. Our findings quantify necessary conditions and detectable consequences of energy expenditure. These richer mathematical behaviors-feasibly accessed using biological energy budgets and rates-may empower cells to accomplish sophisticated regulation with simpler architectures than those required at equilibrium.
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