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KDM2 Family Members are Regulated by HIF-1 in Hypoxia

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 transac...

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Autores principales: Batie, Michael, Druker, Jimena, D’Ignazio, Laura, Rocha, Sonia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5371873/
https://www.ncbi.nlm.nih.gov/pubmed/28304334
http://dx.doi.org/10.3390/cells6010008
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author Batie, Michael
Druker, Jimena
D’Ignazio, Laura
Rocha, Sonia
author_facet Batie, Michael
Druker, Jimena
D’Ignazio, Laura
Rocha, Sonia
author_sort Batie, Michael
collection PubMed
description 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.
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spelling pubmed-53718732017-04-10 KDM2 Family Members are Regulated by HIF-1 in Hypoxia Batie, Michael Druker, Jimena D’Ignazio, Laura Rocha, Sonia Cells Article 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. MDPI 2017-03-17 /pmc/articles/PMC5371873/ /pubmed/28304334 http://dx.doi.org/10.3390/cells6010008 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Batie, Michael
Druker, Jimena
D’Ignazio, Laura
Rocha, Sonia
KDM2 Family Members are Regulated by HIF-1 in Hypoxia
title KDM2 Family Members are Regulated by HIF-1 in Hypoxia
title_full KDM2 Family Members are Regulated by HIF-1 in Hypoxia
title_fullStr KDM2 Family Members are Regulated by HIF-1 in Hypoxia
title_full_unstemmed KDM2 Family Members are Regulated by HIF-1 in Hypoxia
title_short KDM2 Family Members are Regulated by HIF-1 in Hypoxia
title_sort kdm2 family members are regulated by hif-1 in hypoxia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5371873/
https://www.ncbi.nlm.nih.gov/pubmed/28304334
http://dx.doi.org/10.3390/cells6010008
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