Integration of Metabolic and Gene Regulatory Networks Modulates the C. elegans Dietary Response

Expression profiles are tailored according to dietary input. However, the networks that control dietary responses remain largely uncharacterized. Here, we combine forward and reverse genetic screens to delineate a network of 184 genes that affect the C. elegans dietary response to Comamonas DA1877 b...

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Bibliographic Details
Published in:Cell 2013-03, Vol.153 (1), p.253-266
Main Authors: Watson, Emma, MacNeil, Lesley T., Arda, H. Efsun, Zhu, Lihua Julie, Walhout, Albertha J.M.
Format: Article
Language:English
Subjects:
Acyl-CoA Dehydrogenase - metabolism
amino acid metabolism
Animals
bacteria
Betaproteobacteria
Caenorhabditis elegans - metabolism
Caenorhabditis elegans Proteins - metabolism
Comamonas
Diet
enzymes
Escherichia coli
gene expression regulation
Gene Regulatory Networks
Humans
Insulin - metabolism
Metabolic Networks and Pathways
Metabolism, Inborn Errors
mitochondria
Mitochondria - metabolism
mutation
nutritional intervention
Phosphotransferases (Alcohol Group Acceptor) - metabolism
regulator genes
RNA Interference
Signal Transduction
transcription (genetics)
transcription factors
Transcription Factors - metabolism
tricarboxylic acid cycle
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Summary:Expression profiles are tailored according to dietary input. However, the networks that control dietary responses remain largely uncharacterized. Here, we combine forward and reverse genetic screens to delineate a network of 184 genes that affect the C. elegans dietary response to Comamonas DA1877 bacteria. We find that perturbation of a mitochondrial network composed of enzymes involved in amino acid metabolism and the TCA cycle affects the dietary response. In humans, mutations in the corresponding genes cause inborn diseases of amino acid metabolism, most of which are treated by dietary intervention. We identify several transcription factors (TFs) that mediate the changes in gene expression upon metabolic network perturbations. Altogether, our findings unveil a transcriptional response system that is poised to sense dietary cues and metabolic imbalances, illustrating extensive communication between metabolic networks in the mitochondria and gene regulatory networks in the nucleus. [Display omitted] ► Forward and reverse genetic screens uncover diet-response network in C. elegans ► Mutations in human orthologs cause inborn metabolic disorders treated by diet ► Mitochondrial metabolic and nuclear regulatory networks communicate reciprocally ► Multiple transcription factors mediate the metabolic network perturbation response Forward and reverse genetic screens identify a network of metabolic and regulatory genes that affect the response of C. elegans to a diet of Comamonas bacteria. Among the metabolic genes, many encode mitochondrial enzymes that are also implicated in inborn errors of metabolism in humans.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2013.02.050