Hypoxia and hypoxia mimetics differentially modulate histone post-translational modifications
Post-translational modifications (PTMs) to the tails of the core histone proteins are critically involved in epigenetic regulation. Hypoxia affects histone modifications by altering the activities of histone-modifying enzymes and the levels of hypoxia-inducible factor (HIF) isoforms. Synthetic hypox...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2021-01-01
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| Series: | Epigenetics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/15592294.2020.1786305 |
| _version_ | 1797678869763850240 |
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| author | Kuo-Feng Hsu Sarah E. Wilkins Richard J. Hopkinson Rok Sekirnik Emily Flashman Akane Kawamura James S.O. McCullagh Louise J. Walport Christopher J. Schofield |
| author_facet | Kuo-Feng Hsu Sarah E. Wilkins Richard J. Hopkinson Rok Sekirnik Emily Flashman Akane Kawamura James S.O. McCullagh Louise J. Walport Christopher J. Schofield |
| author_sort | Kuo-Feng Hsu |
| collection | DOAJ |
| description | Post-translational modifications (PTMs) to the tails of the core histone proteins are critically involved in epigenetic regulation. Hypoxia affects histone modifications by altering the activities of histone-modifying enzymes and the levels of hypoxia-inducible factor (HIF) isoforms. Synthetic hypoxia mimetics promote a similar response, but how accurately the hypoxia mimetics replicate the effects of limited oxygen availability on the levels of histone PTMs is uncertain. Here we report studies on the profiling of the global changes to PTMs on intact histones in response to hypoxia/hypoxia-related stresses using liquid chromatography-mass spectrometry (LC-MS). We demonstrate that intact protein LC-MS profiling is a relatively simple and robust method for investigating potential effects of drugs on histone modifications. The results provide insights into the profiles of PTMs associated with hypoxia and inform on the extent to which hypoxia and hypoxia mimetics cause similar changes to histones. These findings imply chemically-induced hypoxia does not completely replicate the substantial effects of physiological hypoxia on histone PTMs, highlighting that caution should be used in interpreting data from their use. |
| first_indexed | 2024-03-11T23:06:12Z |
| format | Article |
| id | doaj.art-232fbe08a0724f6ca2a8f27be76d1d05 |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:06:12Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-232fbe08a0724f6ca2a8f27be76d1d052023-09-21T13:09:23ZengTaylor & Francis GroupEpigenetics1559-22941559-23082021-01-01161142710.1080/15592294.2020.17863051786305Hypoxia and hypoxia mimetics differentially modulate histone post-translational modificationsKuo-Feng Hsu0Sarah E. Wilkins1Richard J. Hopkinson2Rok Sekirnik3Emily Flashman4Akane Kawamura5James S.O. McCullagh6Louise J. Walport7Christopher J. Schofield8University of OxfordUniversity of OxfordUniversity of OxfordUniversity of OxfordUniversity of OxfordUniversity of OxfordUniversity of OxfordUniversity of OxfordUniversity of OxfordPost-translational modifications (PTMs) to the tails of the core histone proteins are critically involved in epigenetic regulation. Hypoxia affects histone modifications by altering the activities of histone-modifying enzymes and the levels of hypoxia-inducible factor (HIF) isoforms. Synthetic hypoxia mimetics promote a similar response, but how accurately the hypoxia mimetics replicate the effects of limited oxygen availability on the levels of histone PTMs is uncertain. Here we report studies on the profiling of the global changes to PTMs on intact histones in response to hypoxia/hypoxia-related stresses using liquid chromatography-mass spectrometry (LC-MS). We demonstrate that intact protein LC-MS profiling is a relatively simple and robust method for investigating potential effects of drugs on histone modifications. The results provide insights into the profiles of PTMs associated with hypoxia and inform on the extent to which hypoxia and hypoxia mimetics cause similar changes to histones. These findings imply chemically-induced hypoxia does not completely replicate the substantial effects of physiological hypoxia on histone PTMs, highlighting that caution should be used in interpreting data from their use.http://dx.doi.org/10.1080/15592294.2020.1786305hypoxiahistone post-translational modificationsepigeneticshypoxia mimeticsepigeneticshifintact protein mass spectrometryiron chelating drugs2-oxoglutarate/α-ketoglutarate oxygenases |
| spellingShingle | Kuo-Feng Hsu Sarah E. Wilkins Richard J. Hopkinson Rok Sekirnik Emily Flashman Akane Kawamura James S.O. McCullagh Louise J. Walport Christopher J. Schofield Hypoxia and hypoxia mimetics differentially modulate histone post-translational modifications Epigenetics hypoxia histone post-translational modifications epigenetics hypoxia mimetics epigenetics hif intact protein mass spectrometry iron chelating drugs 2-oxoglutarate/α-ketoglutarate oxygenases |
| title | Hypoxia and hypoxia mimetics differentially modulate histone post-translational modifications |
| title_full | Hypoxia and hypoxia mimetics differentially modulate histone post-translational modifications |
| title_fullStr | Hypoxia and hypoxia mimetics differentially modulate histone post-translational modifications |
| title_full_unstemmed | Hypoxia and hypoxia mimetics differentially modulate histone post-translational modifications |
| title_short | Hypoxia and hypoxia mimetics differentially modulate histone post-translational modifications |
| title_sort | hypoxia and hypoxia mimetics differentially modulate histone post translational modifications |
| topic | hypoxia histone post-translational modifications epigenetics hypoxia mimetics epigenetics hif intact protein mass spectrometry iron chelating drugs 2-oxoglutarate/α-ketoglutarate oxygenases |
| url | http://dx.doi.org/10.1080/15592294.2020.1786305 |
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