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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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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. |
format | Online Article Text |
id | pubmed-5371873 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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