Batie, Michael 
ORCID: 0000-0002-7508-6641, Druker, Jimena, D'Ignazio, Laura and Rocha, Sonia
(2017)
KDM2 Family Members are Regulated by HIF-1 in Hypoxia.
CELLS, 6 (1).
E8-.
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | hypoxia, HIF-1, KDM2, JmjC, drosophila, ChIP |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 10 Jan 2018 10:12 |
| Last Modified: | 19 Jan 2023 06:46 |
| DOI: | 10.3390/cells6010008 |
| Open Access URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC53718... |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3015771 |
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