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...

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Main Authors: Hsu, K-F, Wilkins, S, Hopkinson, R, Sekirnik, R, Flashman, E, Kawamura, A, McCullagh, J, Walport, L, Schofield, C
Format: Journal article
Language:English
Published: Taylor & Francis 2020
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author Hsu, K-F
Wilkins, S
Hopkinson, R
Sekirnik, R
Flashman, E
Kawamura, A
McCullagh, J
Walport, L
Schofield, C
author_facet Hsu, K-F
Wilkins, S
Hopkinson, R
Sekirnik, R
Flashman, E
Kawamura, A
McCullagh, J
Walport, L
Schofield, C
author_sort Hsu, K-F
collection OXFORD
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.
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spelling oxford-uuid:851be63e-d15b-4dc2-a39f-0f85601a858a2022-03-26T21:55:18ZHypoxia and hypoxia mimetics differentially modulate histone post-translational modificationsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:851be63e-d15b-4dc2-a39f-0f85601a858aEnglishSymplectic ElementsTaylor & Francis2020Hsu, K-FWilkins, SHopkinson, RSekirnik, RFlashman, EKawamura, AMcCullagh, JWalport, LSchofield, CPost-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.
spellingShingle Hsu, K-F
Wilkins, S
Hopkinson, R
Sekirnik, R
Flashman, E
Kawamura, A
McCullagh, J
Walport, L
Schofield, C
Hypoxia and hypoxia mimetics differentially modulate histone post-translational modifications
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
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