ArticleProceedings of the National Academy of Sciences of the United States of America2012
Regulatory architecture determines optimal regulation of gene expression in metabolic pathways.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed.
- EngineeringACS synthetic biology · 2026Article
- Transcriptome and miRNAome analysis reveals expression profiles of platycodin biosynthesis-related genes and their potential miRNA regulators inFrontiers in plant science · 2026Article
- The modular biochemical reaction network structure of cellular translation.NPJ systems biology and applications · 2023Article
- Epigenetic and Metabolic Regulation of Macrophages during Gout.Gout, urate, and crystal deposition disease · 2023Article
- Design of Four Small-Molecule-Inducible Systems in the Yeast Chromosome, Applied to Optimize Terpene Biosynthesis.ACS synthetic biology · 2023Article
- The impact of metabolism on the adaptation of organisms to environmental change.Frontiers in cell and developmental biology · 2023Article
- Optimal transcriptional regulation of dynamic bacterial responses to sudden drug exposures.Biophysical journal · 2022Article
- Article
- Dichotomous feedback: a signal sequestration-based feedback mechanism for biocontroller design.Journal of the Royal Society, Interface · 2022Article
- Use of the volatile trichodiene to reduce Fusarium head blight and trichothecene contamination in wheat.Microbial biotechnology · 2022Article
- Metabolome and proteome analyses reveal transcriptional misregulation in glycolysis of engineered E. coli.Nature communications · 2021Article
- Design Principle for Decoding Calcium Signals to Generate Specific Gene Expression Via Transcription.Plant physiology · 2020Article
- Metabolite Sequestration Enables Rapid Recovery from Fatty Acid Depletion in Escherichia coli.mBio · 2020Article
- Computation of Single-Cell Metabolite Distributions Using Mixture Models.Frontiers in cell and developmental biology · 2020Article
- Metabolic profiling of cancer cells reveals genome-wide crosstalk between transcriptional regulators and metabolism.Nature communications · 2019Article
- Allosteric Feedback Inhibition Enables Robust Amino Acid Biosynthesis in E. coli by Enforcing Enzyme Overabundance.Cell systems · 2019Article
- Article
- Dynamic metabolic control: towards precision engineering of metabolism.Journal of industrial microbiology & biotechnology · 2018Article
- Genome-Wide Mapping of Transcriptional Regulation and Metabolism Describes Information-Processing Units inFrontiers in microbiology · 2017Article
- Glucose becomes one of the worst carbon sources for E.coli on poor nitrogen sources due to suboptimal levels of cAMP.Scientific reports · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
In response to environmental changes, the connections ("arrows") in gene regulatory networks determine which genes modulate their expression, but the quantitative parameters of the network ("the numbers on the arrows") are equally important in determining the resulting phenotype. What are the objectives and constraints by which evolution determines these parameters? We explore these issues by analyzing gene expression changes in a number of yeast metabolic pathways in response to nutrient depletion. We find that a striking pattern emerges that couples the regulatory architecture of the pathway to the gene expression response. In particular, we find that pathways controlled by the intermediate metabolite activation (IMA) architecture, in which an intermediate metabolite activates transcription of pathway genes, exhibit the following response: the enzyme immediately downstream of the regulatory metabolite is under the strongest transcriptional control, whereas the induction of the enzymes upstream of the regulatory intermediate is relatively weak. This pattern of responses is absent in pathways not controlled by an IMA architecture. The observation can be explained by the constraint imposed by the fundamental feedback structure of the network, which places downstream enzymes under a negative feedback loop and upstream ones under a positive feedback loop. This general design principle for transcriptional control of a metabolic pathway can be derived from a simple cost/benefit model of gene expression, in which the observed pattern is an optimal solution. Our results suggest that the parameters regulating metabolic enzyme expression are optimized by evolution, under the strong constraint of the underlying regulatory architecture.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.