ArticleProceedings of the National Academy of Sciences of the United States of America2014
Hierarchical expression of genes controlled by the Bacillus subtilis global regulatory protein CodY.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 107 citations in OpenAlex.
- InJournal of bacteriology · 2026Article
- InbioRxiv : the preprint server for biology · 2026Article
- Deciphering strain differences in codY regulation ofMicrobiology spectrum · 2026Article
- Article
- T7 RNA polymerase-guided base editor for accelerated continuous evolution inSynthetic and systems biotechnology · 2025Article
- Inactivation of branched-chain amino acid uptake halts Staphylococcus aureus growth and induces bacterial quiescence within macrophages.PLoS pathogens · 2025Article
- Genomic Insights intoInternational journal of molecular sciences · 2025Article
- The SinR·SlrR Heteromer Attenuates Transcription of a Long Operon of Flagellar Genes in Bacillus subtilis.Journal of molecular biology · 2025Article
- Article
- A megatransposon drives the adaptation of Thermoanaerobacter kivui to carbon monoxide.Nature communications · 2025Article
- CodY controls the SaeR/S two-component system by modulating branched-chain fatty acid synthesis inJournal of bacteriology · 2024Article
- Catabolism of germinant amino acids is required to prevent premature spore germination inmBio · 2024Article
- MOB rules: Antibiotic Exposure Reprograms Metabolism to MobilizebioRxiv : the preprint server for biology · 2024Article
- Airway metabolic profiling during Streptococcus pneumoniae infection identifies branched chain amino acids as signatures of upper airway colonisation.PLoS pathogens · 2023Article
- CodY: An Essential Transcriptional Regulator Involved in Environmental Stress Tolerance in FoodborneFoods (Basel, Switzerland) · 2023Article
- Structural insights into CodY activation and DNA recognition.Nucleic acids research · 2023Article
- Understanding and application of Bacillus nitrogen regulation: A synthetic biology perspective.Journal of advanced research · 2023Review
- Termination factor Rho mediates transcriptional reprogramming of Bacillus subtilis stationary phase.PLoS genetics · 2023Article
- (p)ppGpp - an important player during heat shock response.microLife · 2023Review
- Understanding the Genome-Wide Transcription Response To Various cAMP Levels in Bacteria Using Phenomenological Models.mSystems · 2022Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Global regulators that bind strategic metabolites allow bacteria to adapt rapidly to dynamic environments by coordinating the expression of many genes. We report an approach for determining gene regulation hierarchy using the regulon of the Bacillus subtilis global regulatory protein CodY as proof of principle. In theory, this approach can be used to measure the dynamics of any bacterial transcriptional regulatory network that is affected by interaction with a ligand. In B. subtilis, CodY controls dozens of genes, but the threshold activities of CodY required to regulate each gene are unknown. We hypothesized that targets of CodY are differentially regulated based on varying affinity for the protein's many binding sites. We used RNA sequencing to determine the transcription profiles of B. subtilis strains expressing mutant CodY proteins with different levels of residual activity. In parallel, we quantified intracellular metabolites connected to central metabolism. Strains producing CodY variants F71Y, R61K, and R61H retained varying degrees of partial activity relative to the WT protein, leading to gene-specific, differential alterations in transcript abundance for the 223 identified members of the CodY regulon. Using liquid chromatography coupled to MS, we detected significant increases in branched-chain amino acids and intermediates of arginine, proline, and glutamate metabolism, as well as decreases in pyruvate and glycerate as CodY activity decreased. We conclude that a spectrum of CodY activities leads to programmed regulation of gene expression and an apparent rerouting of carbon and nitrogen metabolism, suggesting that during changes in nutrient availability, CodY prioritizes the expression of specific pathways.
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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.