TY - JOUR TI - Hypoxia-inducible factor cell non-autonomously regulates C. elegans stress responses and behavior via a nuclear receptor AU - Pender, Corinne L AU - Horvitz, H Robert A2 - Kaeberlein, Matt A2 - Stainier, Didier YR VL - 7 PY - 2018 DA - 2018/07/16 SP - e36828 C1 - eLife 2018;7:e36828 DO - 10.7554/eLife.36828 UR - https://doi.org/10.7554/eLife.36828 AB - The HIF (hypoxia-inducible factor) transcription factor is the master regulator of the metazoan response to chronic hypoxia. In addition to promoting adaptations to low oxygen, HIF drives cytoprotective mechanisms in response to stresses and modulates neural circuit function. How most HIF targets act in the control of the diverse aspects of HIF-regulated biology remains unknown. We discovered that a HIF target, the C. elegans gene cyp-36A1, is required for numerous HIF-dependent processes, including modulation of gene expression, stress resistance, and behavior. cyp-36A1 encodes a cytochrome P450 enzyme that we show controls expression of more than a third of HIF-induced genes. CYP-36A1 acts cell non-autonomously by regulating the activity of the nuclear hormone receptor NHR-46, suggesting that CYP-36A1 functions as a biosynthetic enzyme for a hormone ligand of this receptor. We propose that regulation of HIF effectors through activation of cytochrome P450 enzyme/nuclear receptor signaling pathways could similarly occur in humans. KW - hypoxia-inducible factor KW - cytochrome P450 KW - nuclear hormone receptor JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -