ArticleNature microbiology2016
The metabolic background is a global player in Saccharomyces gene expression epistasis.
Article in Nature microbiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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53 citing papers in PubMed, 91 citations in OpenAlex.
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- Transcriptomic and proteomic effects of gene deletion are not evolutionarily conserved.Genome research · 2025Article
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- Metabolic heterogeneity and cross-feeding within isogenic yeast populations captured by DILAC.Nature microbiology · 2023Article
- Controlling gene expression with deep generative design of regulatory DNA.Nature communications · 2022Article
- Growth-rate-dependent and nutrient-specific gene expression resource allocation in fission yeast.Life science alliance · 2022Article
- Give and take in the exometabolome.Nature microbiology · 2022Article
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17 authors at 6 institutions in 4 countries.
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Abstract
The regulation of gene expression in response to nutrient availability is fundamental to the genotype-phenotype relationship. The metabolic-genetic make-up of the cell, as reflected in auxotrophy, is hence likely to be a determinant of gene expression. Here, we address the importance of the metabolic-genetic background by monitoring transcriptome, proteome and metabolome in a repertoire of 16 Saccharomyces cerevisiae laboratory backgrounds, combinatorially perturbed in histidine, leucine, methionine and uracil biosynthesis. The metabolic background affected up to 85% of the coding genome. Suggesting widespread confounding, these transcriptional changes show, on average, 83% overlap between unrelated auxotrophs and 35% with previously published transcriptomes generated for non-metabolic gene knockouts. Background-dependent gene expression correlated with metabolic flux and acted, predominantly through masking or suppression, on 88% of transcriptional interactions epistatically. As a consequence, the deletion of the same metabolic gene in a different background could provoke an entirely different transcriptional response. Propagating to the proteome and scaling up at the metabolome, metabolic background dependencies reveal the prevalence of metabolism-dependent epistasis at all regulatory levels. Urging a fundamental change of the prevailing laboratory practice of using auxotrophs and nutrient supplemented media, these results reveal epistatic intertwining of metabolism with gene expression on the genomic scale.
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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.