title: Integration of metabolic and gene regulatory networks modulates the C. elegans dietary response.
abstract: 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.
authors.affiliation: Program in Systems Biology, University of Massachusetts Medical School, Worcester, MA.|Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA.
authors.forename: Emma
authors.initials: E
authors.lastname: Watson
authors.affiliation: Program in Systems Biology, University of Massachusetts Medical School, Worcester, MA.|Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA.
authors.forename: Lesley T
authors.initials: LT
authors.lastname: MacNeil
authors.affiliation: Program in Systems Biology, University of Massachusetts Medical School, Worcester, MA.|Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA.
authors.forename: H Efsun
authors.initials: HE
authors.lastname: Arda
authors.affiliation: Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA.
authors.forename: Lihua Julie
authors.initials: LJ
authors.lastname: Zhu
authors.affiliation: Program in Systems Biology, University of Massachusetts Medical School, Worcester, MA.|Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA.
authors.forename: Albertha J M
authors.initials: AJM
authors.lastname: Walhout
mesh_terms: D042964:Acyl-CoA Dehydrogenase / Q000378:metabolism; D000818:Animals; D020562:Betaproteobacteria; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D004032:Diet; D004926:Escherichia coli; D053263:Gene Regulatory Networks; D006801:Humans; D007328:Insulin / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D008661:Metabolism, Inborn Errors; D008928:Mitochondria / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D007328:Insulin; D014157:Transcription Factors; D042964:Acyl-CoA Dehydrogenase; D017853:Phosphotransferases (Alcohol Group Acceptor); C472494:let-363 protein, C elegans
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