期刊
EPIGENOMICS
卷 7, 期 5, 页码 791-811出版社
FUTURE MEDICINE LTD
DOI: 10.2217/epi.15.24
关键词
2-oxoglutarate dependent oxygenases; cancer; cardiovascular diseases development; epigenetic regulation; H3; HIF; histone 3; histone demethylases; hypoxia; KDMs; oxygen kinetics; oxygen sensors
资金
- British Heart Foundation Centre of Research Excellence, Oxford [RE/08/004/23915]
- Cancer Research UK [C8717/A18245]
- Royal Society
- Cancer Research UK [18245] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [EP/L003376/1] Funding Source: researchfish
- EPSRC [EP/L003376/1] Funding Source: UKRI
The response to hypoxia is primarily mediated by the hypoxia-inducible transcription factor (HIF). Levels of HIF are regulated by the oxygen-sensing HIF hydroxylases, members of the 2-oxoglutarate (2OG) dependent oxygenase family. JmjC-domain containing histone lysine demethylases (JmjC-KDMs), also members of the 2OG oxygenase family, are key epigenetic regulators that modulate the methylation levels of histone tails. Kinetic studies of the JmjC-KDMs indicate they could also act in an oxygen-sensitive manner. This may have important implications for epigenetic regulation in hypoxia. In this review we examine evidence that the levels and activity of JmjC-KDMs are sensitive to oxygen availability, and consider how this may influence their roles in early development and hypoxic disease states including cancer and cardiovascular disease.
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