PT  - JOURNAL ARTICLE
AU  - Shivani Nanda
AU  - Marc-Antoine Jacques
AU  - Wen Wang
AU  - Chad L Myers
AU  - L. Safak Yilmaz
AU  - Albertha JM Walhout
TI  - Systems-level transcriptional regulation of <em>Caenorhabditis elegans</em> metabolism
AID  - 10.1101/2022.11.08.515576
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.11.08.515576
4099  - http://biorxiv.org/content/early/2022/11/09/2022.11.08.515576.short
4100  - http://biorxiv.org/content/early/2022/11/09/2022.11.08.515576.full
AB  - Metabolism is precisely controlled to ensure organismal development and homeostasis. Several mechanisms regulate metabolism, including allosteric control and transcriptional regulation of metabolic enzymes and transporters. So far, metabolism regulation has mostly been described for individual genes and pathways, and the extent of transcriptional regulation of the entire metabolic network remains largely unknown. Here, we find that more than three-quarters of all metabolic genes are transcriptionally regulated in the nematode Caenorhabditis elegans. We find that many annotated metabolic pathways are coexpressed, and we use gene expression data and the iCEL1314 metabolic network model to define coregulated sub-pathways in an unbiased manner. Using a large gene expression compendium, we determine the conditions where sub-pathways exhibit strong coexpression. Finally, we develop ‘WormClust’, a web application that enables a gene-by-gene query of genes to view their association with metabolic (sub)-pathways. Overall, this study sheds light on the ubiquity of transcriptional regulation of metabolism and provides a blueprint for similar studies in other organisms, including humans.