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Hypoxia and hypoxia mimetics differentially modulate histone post-translational modifications

Lookup NU author(s): Professor Akane Kawamura

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

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.


Publication metadata

Author(s): Hsu KF, Wilkins SE, Hopkinson RJ, Sekirnik R, Flashman E, Kawamura A, McCullagh JSO, Walport L, Schofield CJ

Publication type: Article

Publication status: Published

Journal: Epigenetics

Year: 2020

Issue: ePub ahead of Print

Online publication date: 01/06/2020

Acceptance date: 22/05/2020

Date deposited: 08/07/2020

ISSN (print): 1559-2294

ISSN (electronic): 1559-2308

Publisher: Taylor & Francis

URL: https://doi.org/10.1080/15592294.2020.1786305

DOI: 10.1080/15592294.2020.1786305


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