ArticleProceedings of the National Academy of Sciences of the United States of America2023
Competing constraints shape the nonequilibrium limits of cellular decision-making.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 19 citations in OpenAlex.
- 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
- A fundamental trade-off among noise suppression, response sensitivity and speed in biological feedback networks.NPJ systems biology and applications · 2026Article
- Highly Constrained Kinetic Models for Single-Cell Gene Expression Analysis.bioRxiv : the preprint server for biology · 2026Article
- A unified computational framework for quantitative design and optimization of transcriptional regulation across bacterial species.Nucleic acids research · 2026Article
- Algebraic formulas for first-passage times of Markov processes in the linear framework.Bulletin of mathematical biology · 2025Article
- Limits on the computational expressivity of non-equilibrium biophysical processes.Nature communications · 2025Article
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- A differentiable Gillespie algorithm for simulating chemical kinetics, parameter estimation, and designing synthetic biological circuits.bioRxiv : the preprint server for biology · 2025Article
- Article
- Chromatin enables precise and scalable gene regulation with factors of limited specificity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Flexibility and sensitivity in gene regulation out of equilibrium.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Energy Aware Technology Mapping of Genetic Logic Circuits.ACS synthetic biology · 2024Article
- Energy Aware Technology Mapping of Genetic Logic Circuits.bioRxiv : the preprint server for biology · 2024Article
- Governing principles of transcriptional logic out of equilibrium.Biophysical journal · 2024Article
- Time will tell: comparing timescales to gain insight into transcriptional bursting.Trends in genetics : TIG · 2024Review
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
Gene regulation is central to cellular function. Yet, despite decades of work, we lack quantitative models that can predict how transcriptional control emerges from molecular interactions at the gene locus. Thermodynamic models of transcription, which assume that gene circuits operate at equilibrium, have previously been employed with considerable success in the context of bacterial systems. However, the presence of ATP-dependent processes within the eukaryotic transcriptional cycle suggests that equilibrium models may be insufficient to capture how eukaryotic gene circuits sense and respond to input transcription factor concentrations. Here, we employ simple kinetic models of transcription to investigate how energy dissipation within the transcriptional cycle impacts the rate at which genes transmit information and drive cellular decisions. We find that biologically plausible levels of energy input can lead to significant gains in how rapidly gene loci transmit information but discover that the regulatory mechanisms underlying these gains change depending on the level of interference from noncognate activator binding. When interference is low, information is maximized by harnessing energy to push the sensitivity of the transcriptional response to input transcription factors beyond its equilibrium limits. Conversely, when interference is high, conditions favor genes that harness energy to increase transcriptional specificity by proofreading activator identity. Our analysis further reveals that equilibrium gene regulatory mechanisms break down as transcriptional interference increases, suggesting that energy dissipation may be indispensable in systems where noncognate factor interference is sufficiently large.
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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.