Hypoxia-inducible factor cell non-autonomously regulates C. elegans stress responses and behavior via a nuclear receptor
Name
elife-36828-v2.pdf
Description
Published version
Size
2.99 MB
Format
Adobe PDF
Checksum (MD5)
c1c686c130cf6a0b171714a7462342c9
Author(s)
Pender, Corinne Lenore
Horvitz, Howard Robert
Date Issued
July 2018
Journal
eLIfe
Publisher
eLife Sciences Publications, Ltd
Citation
Pender, Corrine L. and H. Robert Horvitz. "Hypoxia-inducible factor cell non-autonomously regulates C. elegans stress responses and behavior via a nuclear receptor." eLife 7 (July 2018): e36828 © 2018 Pender and Horvitz
Version
Final published version
Abstract
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-36A1encodes 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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
McGovern Institute for Brain Research at MIT
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.7554/elife.36828
