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The S. pombe Histone H2A Dioxygenase Ofd2 Regulates Gene Expression during Hypoxia
Post-translational modification of histone proteins are known to play an important role in regulating chromatin structure. In an effort to find additional histone modifications we set out to screen enzymes of the 2-oxoglutarate and Fe(II)-dependent (2-OG-Fe(II)) dioxygenase family for activity towar...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3250473/ https://www.ncbi.nlm.nih.gov/pubmed/22235339 http://dx.doi.org/10.1371/journal.pone.0029765 |
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author | Lando, David Balmer, Jenny Laue, Ernest D. Kouzarides, Tony |
author_facet | Lando, David Balmer, Jenny Laue, Ernest D. Kouzarides, Tony |
author_sort | Lando, David |
collection | PubMed |
description | Post-translational modification of histone proteins are known to play an important role in regulating chromatin structure. In an effort to find additional histone modifications we set out to screen enzymes of the 2-oxoglutarate and Fe(II)-dependent (2-OG-Fe(II)) dioxygenase family for activity towards histones. Here we show that the Schizosaccharomyces pombe 2-OG-Fe(II) dioxygenase domain containing protein-2 (Ofd2) is a histone H2A dioxygenase enzyme. Using a combination of peptide screening and alanine scanning substitution analysis, we identify an HxxLR motif in H2A as a substrate for Ofd2 activity. Transcriptional profiling indicates that Ofd2 regulates the repression of oxidative phosphorylation genes during hypoxic stress. We show that Ofd2 is recruited to the 5′ end of oxidative phosphorylation genes specifically during hypoxia and that it uses its dioxygenase activity to regulate their transcription. Together, these data uncover a novel histone H2A modifying activity involved in the regulation of gene expression during hypoxia. |
format | Online Article Text |
id | pubmed-3250473 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-32504732012-01-10 The S. pombe Histone H2A Dioxygenase Ofd2 Regulates Gene Expression during Hypoxia Lando, David Balmer, Jenny Laue, Ernest D. Kouzarides, Tony PLoS One Research Article Post-translational modification of histone proteins are known to play an important role in regulating chromatin structure. In an effort to find additional histone modifications we set out to screen enzymes of the 2-oxoglutarate and Fe(II)-dependent (2-OG-Fe(II)) dioxygenase family for activity towards histones. Here we show that the Schizosaccharomyces pombe 2-OG-Fe(II) dioxygenase domain containing protein-2 (Ofd2) is a histone H2A dioxygenase enzyme. Using a combination of peptide screening and alanine scanning substitution analysis, we identify an HxxLR motif in H2A as a substrate for Ofd2 activity. Transcriptional profiling indicates that Ofd2 regulates the repression of oxidative phosphorylation genes during hypoxic stress. We show that Ofd2 is recruited to the 5′ end of oxidative phosphorylation genes specifically during hypoxia and that it uses its dioxygenase activity to regulate their transcription. Together, these data uncover a novel histone H2A modifying activity involved in the regulation of gene expression during hypoxia. Public Library of Science 2012-01-03 /pmc/articles/PMC3250473/ /pubmed/22235339 http://dx.doi.org/10.1371/journal.pone.0029765 Text en Lando et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Lando, David Balmer, Jenny Laue, Ernest D. Kouzarides, Tony The S. pombe Histone H2A Dioxygenase Ofd2 Regulates Gene Expression during Hypoxia |
title | The S. pombe Histone H2A Dioxygenase Ofd2 Regulates Gene Expression during Hypoxia |
title_full | The S. pombe Histone H2A Dioxygenase Ofd2 Regulates Gene Expression during Hypoxia |
title_fullStr | The S. pombe Histone H2A Dioxygenase Ofd2 Regulates Gene Expression during Hypoxia |
title_full_unstemmed | The S. pombe Histone H2A Dioxygenase Ofd2 Regulates Gene Expression during Hypoxia |
title_short | The S. pombe Histone H2A Dioxygenase Ofd2 Regulates Gene Expression during Hypoxia |
title_sort | s. pombe histone h2a dioxygenase ofd2 regulates gene expression during hypoxia |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3250473/ https://www.ncbi.nlm.nih.gov/pubmed/22235339 http://dx.doi.org/10.1371/journal.pone.0029765 |
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