A Metabolic Regulatory Network for the C. elegans Intestine

Metabolic perturbations can rewire metabolism under different physiological or pathological conditions, in part by transcriptional mechanisms. While numerous efforts have measured gene expression in response to individual metabolic perturbations, methods that determine all metabolic perturbations that affect the expression for a given gene or set of genes have not been available. Here, we use a gene-centered approach to derive a first-pass metabolic regulatory network for Caenorhabditis elegans by performing RNAi of more than 1,400 metabolic genes with a set of 19 promoter reporter strains that express a fluorescent protein in the intestine. We find that metabolic perturbations generally increase promoter activity, which contrasts with transcription factor TF RNAi, which tends to repress promoter activity. We identify several TFs that modulate promoter activity in response to perturbations of the electron transport chain. This work provides a blueprint for a systems-level understanding of how metabolism affects gene expression, and vice versa. Overall design: C. elegans RNA-sequencing of three experiments. Animals (L1) were treated with 0.3µM Antimycin A & DMSO control until adult stage in biological triplicate.