PXD001491

PXD001491 is an original dataset announced via ProteomeXchange.

Title	The metabolic background is a global player in Saccharomyces gene expression epistasis
Description	The transcriptome, proteome and metabolome of 16 S.cerevisiae backgrounds, combinatorially perturbed in HIS3, LEU2, URA3 and MET15strains are compared. The project was jointly supervised by Kathryn Lilley and Markus Ralser. Transcriptome data has been deposited at ArrayExpress under accession E-MTAB-3991. Metabolome data has been deposited at Metabolights with accession number MTBLS168. 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.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:48:50.882.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Pavel Shliaha
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	iodoacetamide derivatized residue
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2014-11-13 23:28:16	ID requested
1	2016-01-05 11:18:02	announced
2	2016-03-09 02:34:42	announced	Updated publication reference for DOI(s): 10.1038/nmicrobiol.2015.30.
3	2016-03-10 00:30:41	announced	Updated project metadata.
4	2016-08-02 00:31:57	announced	Updated project metadata.
⏵ 5	2023-11-14 08:48:51	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

curator keyword: Biological

submitter keyword: S. cerevisiae

Kathryn Lilley
contact affiliation	Cambridge Centre for Proteomics, Department of Biochemistry, University of Cambridge, Cambridge, U.K.
contact email	ksl23@cam.ac.uk
lab head
Pavel Shliaha
contact affiliation	Cambridge Center For Proteomics
contact email	pvs22@cam.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD001491
     1. Label: PRIDE project
     2. Name: The metabolic background is a global player in Saccharomyces gene expression epistasis