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The metabolic background is a global player in Saccharomyces gene expression epistasis

Item Type:Article
Title:The metabolic background is a global player in Saccharomyces gene expression epistasis
Creators Name:Alam, M.T. and Zelezniak, A. and Mülleder, M. and Shliaha, P. and Schwarz, R. and Capuano, F. and Vowinckel, J. and Radmaneshfar, E. and Krüger, A. and Calvani, E. and Michel, S. and Börno, S. and Christen, S. and Patil, K.R. and Timmermann, B. and Lilley, K.S. and Ralser, M.
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.
Keywords:Fungal Gene Expression Regulation, Gene Regulatory Networks, Genetic Epistasis, Metabolism, Saccharomyces cerevisiae
Source:Nature Microbiology
Publisher:Nature Publishing Group
Page Range:15030
Date:1 February 2016
Official Publication:https://doi.org/10.1038/nmicrobiol.2015.30
PubMed:View item in PubMed

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