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Cells 2017, 6(1), 8; doi:10.3390/cells6010008

KDM2 Family Members are Regulated by HIF-1 in Hypoxia

Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dow street, Dundee DD1 5EH, UK
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Received: 31 October 2016 / Revised: 1 March 2017 / Accepted: 14 March 2017 / Published: 17 March 2017
(This article belongs to the Section Cell Nuclei: Function, Transport and Receptors)
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Abstract

Hypoxia is not only a developmental cue but also a stress and pathological stimulus in many human diseases. The response to hypoxia at the cellular level relies on the activity of the transcription factor family, hypoxia inducible factor (HIF). HIF-1 is responsible for the acute response and transactivates a variety of genes involved in cellular metabolism, cell death, and cell growth. Here, we show that hypoxia results in increased mRNA levels for human lysine (K)-specific demethylase 2 (KDM2) family members, KDM2A and KDM2B, and also for Drosophila melanogaster KDM2, a histone and protein demethylase. In human cells, KDM2 family member’s mRNA levels are regulated by HIF-1 but not HIF-2 in hypoxia. Interestingly, only KDM2A protein levels are significantly induced in a HIF-1-dependent manner, while KDM2B protein changes in a cell type-dependent manner. Importantly, we demonstrate that in human cells, KDM2A regulation by hypoxia and HIF-1 occurs at the level of promoter, with HIF-1 binding to the KDM2A promoter being required for RNA polymerase II recruitment. Taken together, these results demonstrate that KDM2 is a novel HIF target that can help coordinate the cellular response to hypoxia. In addition, these results might explain why KDM2 levels are often deregulated in human cancers. View Full-Text
Keywords: hypoxia; HIF-1; KDM2; JmjC; drosophila; ChIP hypoxia; HIF-1; KDM2; JmjC; drosophila; ChIP
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Batie, M.; Druker, J.; D’Ignazio, L.; Rocha, S. KDM2 Family Members are Regulated by HIF-1 in Hypoxia. Cells 2017, 6, 8.

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