Hypoxia-inducible factor cell non-autonomously regulates C. elegans stress responses and behavior via a nuclear receptor
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 ac...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications, Ltd
2020
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| Online Access: | https://hdl.handle.net/1721.1/126077 |
| _version_ | 1811095152288071680 |
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| author | Pender, Corinne Lenore Horvitz, Howard Robert |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Pender, Corinne Lenore Horvitz, Howard Robert |
| author_sort | Pender, Corinne Lenore |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T16:11:29Z |
| format | Article |
| id | mit-1721.1/126077 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T16:11:29Z |
| publishDate | 2020 |
| publisher | eLife Sciences Publications, Ltd |
| record_format | dspace |
| spelling | mit-1721.1/1260772022-10-02T06:57:13Z Hypoxia-inducible factor cell non-autonomously regulates C. elegans stress responses and behavior via a nuclear receptor Pender, Corinne Lenore Horvitz, Howard Robert Massachusetts Institute of Technology. Department of Biology McGovern Institute for Brain Research at MIT Koch Institute for Integrative Cancer Research at MIT 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. National Institutes of Health (Grant GM024663) National Institutes of Health (Grant T32GM007287) 2020-07-07T19:36:28Z 2020-07-07T19:36:28Z 2018-07 2018-03 2019-12-05T18:26:02Z Article http://purl.org/eprint/type/JournalArticle 2050-084X https://hdl.handle.net/1721.1/126077 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 en http://dx.doi.org/10.7554/elife.36828 eLIfe Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf eLife Sciences Publications, Ltd eLife |
| spellingShingle | Pender, Corinne Lenore Horvitz, Howard Robert Hypoxia-inducible factor cell non-autonomously regulates C. elegans stress responses and behavior via a nuclear receptor |
| title | Hypoxia-inducible factor cell non-autonomously regulates C. elegans stress responses and behavior via a nuclear receptor |
| title_full | Hypoxia-inducible factor cell non-autonomously regulates C. elegans stress responses and behavior via a nuclear receptor |
| title_fullStr | Hypoxia-inducible factor cell non-autonomously regulates C. elegans stress responses and behavior via a nuclear receptor |
| title_full_unstemmed | Hypoxia-inducible factor cell non-autonomously regulates C. elegans stress responses and behavior via a nuclear receptor |
| title_short | Hypoxia-inducible factor cell non-autonomously regulates C. elegans stress responses and behavior via a nuclear receptor |
| title_sort | hypoxia inducible factor cell non autonomously regulates c elegans stress responses and behavior via a nuclear receptor |
| url | https://hdl.handle.net/1721.1/126077 |
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