Projects per year
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 language | English |
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Pages (from-to) | 1222-1226 |
Number of pages | 5 |
Journal | Science |
Volume | 363 |
Issue number | 6432 |
DOIs | |
Publication status | Published - 15 Mar 2019 |
ASJC Scopus subject areas
- General
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Dive into the research topics of 'Hypoxia induces rapid changes to histone methylation and reprograms chromatin'. Together they form a unique fingerprint.Projects
- 2 Finished
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The Interplay Between Oxygen Sensors PHDs and the Cell Cycle (Joint with University of Liverpool)
Fleming, S. (Investigator), Lamond, A. (Investigator) & Swedlow, J. (Investigator)
1/09/17 → 31/08/24
Project: Research
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Strategic Award: Wellcome Trust Technology Platform
Blow, J. (Investigator), Lamond, A. (Investigator) & Owen-Hughes, T. (Investigator)
1/01/13 → 30/09/18
Project: Research