Hypoxia induces rapid changes to histone methylation and reprograms chromatin

Michael Batie, Julianty Frost, Mark Frost, James W. Wilson, Pieta Schofield, Sonia Rocha (Lead / Corresponding author)

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26 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1222-1226
Number of pages5
JournalScience
Volume363
Issue number6432
DOIs
Publication statusPublished - 15 Mar 2019

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Batie, M., Frost, J., Frost, M., Wilson, J. W., Schofield, P., & Rocha, S. (2019). Hypoxia induces rapid changes to histone methylation and reprograms chromatin. Science, 363(6432), 1222-1226. https://doi.org/10.1126/science.aau5870