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JMJD-1.2 controls multiple histone post-translational modifications in germ cells and protects the genome from replication stress

Post-translational modifications of histones, constitutive components of chromatin, regulate chromatin compaction and control all DNA-based cellular processes. C. elegans JMJD-1.2, a member of the KDM7 family, is a demethylase active towards several lysine residues on Histone 3 (H3), but its contrib...

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Autores principales: Myers, Toshia R., Amendola, Pier Giorgio, Lussi, Yvonne C., Salcini, Anna Elisabetta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830613/
https://www.ncbi.nlm.nih.gov/pubmed/29491442
http://dx.doi.org/10.1038/s41598-018-21914-9
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author Myers, Toshia R.
Amendola, Pier Giorgio
Lussi, Yvonne C.
Salcini, Anna Elisabetta
author_facet Myers, Toshia R.
Amendola, Pier Giorgio
Lussi, Yvonne C.
Salcini, Anna Elisabetta
author_sort Myers, Toshia R.
collection PubMed
description Post-translational modifications of histones, constitutive components of chromatin, regulate chromatin compaction and control all DNA-based cellular processes. C. elegans JMJD-1.2, a member of the KDM7 family, is a demethylase active towards several lysine residues on Histone 3 (H3), but its contribution in regulating histone methylation in germ cells has not been fully investigated. Here, we show that jmjd-1.2 is expressed abundantly in the germline where it controls the level of histone 3 lysine 9, lysine 23 and lysine 27 di-methylation (H3K9/K23/K27me2) both in mitotic and meiotic cells. Loss of jmjd-1.2 is not associated with major defects in the germ cells in animals grown under normal conditions or after DNA damage induced by UV or ionizing irradiation. However, jmjd-1.2 mutants are more sensitive to replication stress and the progeny of mutant animals exposed to hydroxyurea show increased embryonic lethality and mutational rate, compared to wild-type. Thus, our results suggest a role for jmjd-1.2 in the maintenance of genome integrity after replication stress and emphasize the relevance of the regulation of histone methylation in genomic stability.
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spelling pubmed-58306132018-03-05 JMJD-1.2 controls multiple histone post-translational modifications in germ cells and protects the genome from replication stress Myers, Toshia R. Amendola, Pier Giorgio Lussi, Yvonne C. Salcini, Anna Elisabetta Sci Rep Article Post-translational modifications of histones, constitutive components of chromatin, regulate chromatin compaction and control all DNA-based cellular processes. C. elegans JMJD-1.2, a member of the KDM7 family, is a demethylase active towards several lysine residues on Histone 3 (H3), but its contribution in regulating histone methylation in germ cells has not been fully investigated. Here, we show that jmjd-1.2 is expressed abundantly in the germline where it controls the level of histone 3 lysine 9, lysine 23 and lysine 27 di-methylation (H3K9/K23/K27me2) both in mitotic and meiotic cells. Loss of jmjd-1.2 is not associated with major defects in the germ cells in animals grown under normal conditions or after DNA damage induced by UV or ionizing irradiation. However, jmjd-1.2 mutants are more sensitive to replication stress and the progeny of mutant animals exposed to hydroxyurea show increased embryonic lethality and mutational rate, compared to wild-type. Thus, our results suggest a role for jmjd-1.2 in the maintenance of genome integrity after replication stress and emphasize the relevance of the regulation of histone methylation in genomic stability. Nature Publishing Group UK 2018-02-28 /pmc/articles/PMC5830613/ /pubmed/29491442 http://dx.doi.org/10.1038/s41598-018-21914-9 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Myers, Toshia R.
Amendola, Pier Giorgio
Lussi, Yvonne C.
Salcini, Anna Elisabetta
JMJD-1.2 controls multiple histone post-translational modifications in germ cells and protects the genome from replication stress
title JMJD-1.2 controls multiple histone post-translational modifications in germ cells and protects the genome from replication stress
title_full JMJD-1.2 controls multiple histone post-translational modifications in germ cells and protects the genome from replication stress
title_fullStr JMJD-1.2 controls multiple histone post-translational modifications in germ cells and protects the genome from replication stress
title_full_unstemmed JMJD-1.2 controls multiple histone post-translational modifications in germ cells and protects the genome from replication stress
title_short JMJD-1.2 controls multiple histone post-translational modifications in germ cells and protects the genome from replication stress
title_sort jmjd-1.2 controls multiple histone post-translational modifications in germ cells and protects the genome from replication stress
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830613/
https://www.ncbi.nlm.nih.gov/pubmed/29491442
http://dx.doi.org/10.1038/s41598-018-21914-9
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