Development is an energy-intensive process that requires dynamic regulation of gene and protein expression. However, the extent to which gene regulatory networks are tuned to metabolic activity remains poorly understood. Richard Carthew and colleagues have previously shown coupling between gene expression dynamics and energy budget – finding that repressors of gene expression become less important under conditions of low metabolic rate. They now set out to explore other relationships between gene regulation and metabolism, both computationally and experimentally. First, they show in silico that activators of gene expression are also less important for dynamic gene regulation when energy expenditure is reduced, but that target gene expression is more sensitive to activator loss under conditions of high metabolic rate. The authors then test these findings experimentally, using EGFR-dependent expression of the Yan protein in the Drosophila eye as a model. Consistent with their computational predictions, they find that Yan is less sensitive to reduced EGFR input under conditions of low metabolic rate, but more sensitive when metabolism is elevated. Consequently, the phenotypic consequences of reduced EGFR signalling are exacerbated under these conditions. These data suggest that gene regulation and metabolic activity are coupled in a way that might tune expression dynamics in response to environmental nutrient availability or other metabolic perturbations.
