Integration of Metabolic and Gene Regulatory Networks Modulates the C. elegans Dietary Response
Program in Systems Biology; Program in Gene Function and Expression; Program in Molecular Medicine
Gene Regulatory Networks; Metabolic Networks and Pathways; Caenorhabditis elegans
Biochemical Phenomena, Metabolism, and Nutrition | Genetics and Genomics | Systems Biology
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.
DOI of Published Version
Cell. 2013 Mar 28;153(1):253-66. doi: 10.1016/j.cell.2013.02.050. Link to article on publisher's site
Watson, Emma; MacNeil, Lesley T.; Arda, H. Efsun; Zhu, Lihua Julie; and Walhout, Albertha J. M., "Integration of Metabolic and Gene Regulatory Networks Modulates the C. elegans Dietary Response" (2013). Program in Systems Biology Publications and Presentations. 21.