Hypoxia Induces Rapid Changes to Histone Methylation and Reprograms Chromatin

Batie, Michael ORCID: 0000-0002-7508-6641, Frost, Julianty ORCID: 0000-0001-8209-2575, Frost, Mark ORCID: 0000-0001-7209-2897, Wilson, James W ORCID: 0000-0002-9373-6919, Schofield, Pieta ORCID: 0000-0002-6398-2537 and Rocha, Sonia
(2019) Hypoxia Induces Rapid Changes to Histone Methylation and Reprograms Chromatin. Science, 363 (6432). pp. 1222-1226.

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Oxygen sensing revisited The cellular response to hypoxia (oxygen deficiency) is a contributing factor in many human diseases. Previous studies examining the way in which hypoxia alters gene expression have focused on oxygen-sensing enzymes that regulate the activity of a transcription factor called hypoxia-inducible factor (see the Perspective by Gallipoli and Huntly). Chakraborty et al. and Batie et al. now show that hypoxia can also affect gene expression through direct effects on chromatin regulators. Certain histone demethylases, such as KDM6A and KDM5A, were found to be direct sensors of oxygen. In cell-culture models, hypoxia diminished the activity of these enzymes and caused changes in the expression of genes that govern cell fate. Science, this issue p. 1217, p. 1222; see also p. 1148 Oxygen is essential for the life of most multicellular organisms. Cells possess enzymes called molecular dioxygenases that depend on oxygen for activity. A subclass of molecular dioxygenases is the histone demethylase enzymes, which are characterized by the presence of a Jumanji-C (JmjC) domain. Hypoxia can alter chromatin, but whether this is a direct effect on JmjC-histone demethylases or due to other mechanisms is unknown. Here, we report that hypoxia induces a rapid and hypoxia-inducible factor–independent induction of histone methylation in a range of human cultured cells. Genomic locations of histone-3 lysine-4 trimethylation (H3K4me3) and H3K36me3 after a brief exposure of cultured cells to hypoxia predict the cell’s transcriptional response several hours later. We show that inactivation of one of the JmjC-containing enzymes, lysine demethylase 5A (KDM5A), mimics hypoxia-induced cellular responses. These results demonstrate that oxygen sensing by chromatin occurs via JmjC-histone demethylase inhibition. Certain chromatin regulators can directly sense changes in oxygen levels, leading to changes in gene expression. Certain chromatin regulators can directly sense changes in oxygen levels, leading to changes in gene expression.

Item Type: Article
Additional Information: copyright: Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. http://www.sciencemag.org/about/science-licenses-journal-article-reuseThis is an article distributed under the terms of the Science Journals Default License. file: M:\Zotero\storage\QGWARSF6\Batie et al. - 2019 - Hypoxia induces rapid changes to histone methylati.pdf;M:\Zotero\storage\3G83NV4Y\1222.html pmid: 30872526
Uncontrolled Keywords: Hela Cells, Chromatin, Fibroblasts, Animals, Humans, Oxygen, Lysine, Amino Acids, Dicarboxylic, Histones, Cell Hypoxia, Methylation, Retinoblastoma-Binding Protein 2, Protein Domains
Depositing User: Symplectic Admin
Date Deposited: 06 Jun 2019 13:56
Last Modified: 02 Jan 2024 08:26
DOI: 10.1126/science.aau5870
Open Access URL: https://www.biorxiv.org/content/10.1101/513069v1
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3041461