Competing constraints shape the nonequilibrium limits of cellular decision-making Article Swipe
Nicholas C Lammers
,
Avi I. Flamholz
,
Hernán G. García
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1073/pnas.2211203120
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1073/pnas.2211203120
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.
Related Topics
Concepts
Biology
Transcription factor
RNA interference
Gene
Genetics
Regulation of gene expression
Computational biology
Activator (genetics)
Transcription (linguistics)
Transcriptional regulation
Cell biology
RNA
Philosophy
Linguistics
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1073/pnas.2211203120
- OA Status
- hybrid
- Cited By
- 17
- References
- 56
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4322757207
All OpenAlex metadata
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- OpenAlex ID
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https://openalex.org/W4322757207Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1073/pnas.2211203120Digital Object Identifier
- Title
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Competing constraints shape the nonequilibrium limits of cellular decision-makingWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
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2023-03-02Full publication date if available
- Authors
-
Nicholas C Lammers, Avi I. Flamholz, Hernán G. GarcíaList of authors in order
- Landing page
-
https://doi.org/10.1073/pnas.2211203120Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.1073/pnas.2211203120Direct OA link when available
- Concepts
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Biology, Transcription factor, RNA interference, Gene, Genetics, Regulation of gene expression, Computational biology, Activator (genetics), Transcription (linguistics), Transcriptional regulation, Cell biology, RNA, Philosophy, LinguisticsTop concepts (fields/topics) attached by OpenAlex
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-
17Total citation count in OpenAlex
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2025: 6, 2024: 9, 2023: 2Per-year citation counts (last 5 years)
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56Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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