GSE123531
Transcriptional redirection of activated SKN-1/NRF2 abates the negative metabolic outcomes of a perceived pathogen infection
Optimal health requires perpetual transcriptional fidelity of gene expression.  SKN-1/NRF2 is a cytoprotective transcription factor in C. elegans that regulates the expression of cellular defenses during stress, including: nutrient deprivation, redox imbalance, and xenobiotic and pathogen exposure. Constitutive activation of SKN-1 results in pleiotropic outcomes, including shortened lifespan and protective redistribution of somatic fat to the germline.  We measured lipid distribution between the soma and germ tissues after manipulation of SKN-1 activity.  Modulating the epigenetic landscape refines SKN-1 activity away from innate immunity targets and alleviates negative metabolic outcomes.  Similarly, paraquat exposure redirects SKN-1 activity toward oxidative stress responses and away from pathogen response genes, which restores lipid distribution across tissues.  Lastly, activating p38 MAPK signaling is sufficient to drive SKN-1-dependent loss of somatic fat.  These data reveal a coordination of organismal metabolic homeostasis with pathogen responses and identifies mechanisms for counteracting the pleiotropic consequences of aberrant transcriptional activity. Overall design: Our study aim to look at transcriptional signatures that changes in Day 3 adults, when loss of fat phenotype occurs in constitutively active SKN-1 worms compared to wild type. We are also interested in transcriptional changes when that loss of fat phenotype is suppressed by paraquat exposure or chromatin restriction.