Journal
G3-GENES GENOMES GENETICS
Volume 3, Issue 11, Pages 1979-1995Publisher
GENETICS SOCIETY AMERICA
DOI: 10.1534/g3.113.006601
Keywords
integrated systems biology; lipid metabolism; regulation; metabolome; omics
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Funding
- Danish Research Agency for Technology and Production, Nature and Universe
- NSF [0504168]
- National Institutes of Health [GM081450]
- Thai Graduate Student Institute Science and Technology (TGIST)
- Office Of The Director
- Office Of Internatl Science &Engineering [0504168] Funding Source: National Science Foundation
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Lipids play a central role in cellular function as constituents of membranes, as signaling molecules, and as storage materials. Although much is known about the role of lipids in regulating specific steps of metabolism, comprehensive studies integrating genome-wide expression data, metabolite levels, and lipid levels are currently lacking. Here, we map condition-dependent regulation controlling lipid metabolism in Saccharomyces cerevisiae by measuring 5636 mRNAs, 50 metabolites, 97 lipids, and 57 C-13-reaction fluxes in yeast using a three-factor full-factorial design. Correlation analysis across eight environmental conditions revealed 2279 gene expression level-metabolite/lipid relationships that characterize the extent of transcriptional regulation in lipid metabolism relative to major metabolic hubs within the cell. To query this network, we developed integrative methods for correlation of multi-omics datasets that elucidate global regulatory signatures. Our data highlight many characterized regulators of lipid metabolism and reveal that sterols are regulated more at the transcriptional level than are amino acids. Beyond providing insights into the systems-level organization of lipid metabolism, we anticipate that our dataset and approach can join an emerging number of studies to be widely used for interrogating cellular systems through the combination of mathematical modeling and experimental biology.
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