A Persistence Detector for Metabolic Network Rewiring in an Animal

ABSTRACT: Biological systems must possess mechanisms that prevent inappropriate responses to spurious environmental inputs. Caenorhabditis elegans has two breakdown pathways for the short-chain fatty acid propionate: a canonical, vitamin B12-dependent pathway and a propionate-shunt that is used when vitamin B12 levels are low. The shunt pathway is kept off when there is sufficient flux through the canonical pathway, likely to avoid generating shunt-specific toxic intermediates. Here, we discover a transcriptional regulatory circuit that activates shunt gene expression upon propionate buildup. The nuclear hormone receptors NHR-10 and NHR-68 function together as a ‘persistence detector’ in a type 1, coherent feed-forward loop with an AND-logic gate to delay shunt activation upon propionate accumulation, and to avoid spurious shunt activation in response to a non-sustained pulse of propionate. Together, our findings identify the first persistence detector in an animal, which transcriptionally rewires propionate metabolism to maintain homeostasis.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE123507 | GEO | 2018/12/08

REPOSITORIES: GEO