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

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Item Type:	Article
Title:	The metabolic background is a global player in Saccharomyces gene expression epistasis
Creators Name:	Alam, M.T., Zelezniak, A., Mülleder, M., Shliaha, P., Schwarz, R., Capuano, F., Vowinckel, J., Radmaneshfar, E., Krüger, A., Calvani, E., Michel, S., Börno, S., Christen, S., Patil, K.R., Timmermann, B., 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
ISSN:	2058-5276
Publisher:	Nature Publishing Group
Volume:	1
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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