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The histone variant H2A.Bbd is enriched at sites of DNA synthesis
Histone variants play an important role in shaping the mammalian epigenome and their aberrant expression is frequently observed in several types of cancer. However, the mechanisms that mediate their function and the composition of the variant-containing chromatin are still largely unknown. A proteom...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041467/ https://www.ncbi.nlm.nih.gov/pubmed/24753410 http://dx.doi.org/10.1093/nar/gku303 |
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author | Sansoni, Viola Casas-Delucchi, Corella S. Rajan, Malini Schmidt, Andreas Bönisch, Clemens Thomae, Andreas W. Staege, Martin S. Hake, Sandra B. Cardoso, M. Cristina Imhof, Axel |
author_facet | Sansoni, Viola Casas-Delucchi, Corella S. Rajan, Malini Schmidt, Andreas Bönisch, Clemens Thomae, Andreas W. Staege, Martin S. Hake, Sandra B. Cardoso, M. Cristina Imhof, Axel |
author_sort | Sansoni, Viola |
collection | PubMed |
description | Histone variants play an important role in shaping the mammalian epigenome and their aberrant expression is frequently observed in several types of cancer. However, the mechanisms that mediate their function and the composition of the variant-containing chromatin are still largely unknown. A proteomic interrogation of chromatin containing the different H2A variants macroH2A.1.2, H2A.Bbd and H2A revealed a strikingly different protein composition. Gene ontology analysis reveals a strong enrichment of splicing factors as well as components of the mammalian replisome in H2A.Bbd-containing chromatin. We find H2A.Bbd localizing transiently to sites of DNA synthesis during S-phase and during DNA repair. Cells that express H2A.Bbd have a shortened S-phase and are more susceptible to DNA damage, two phenotypes that are also observed in human Hodgkin's lymphoma cells that aberrantly express this variant. Based on our experiments we conclude that H2A.Bbd is targeted to newly synthesized DNA during replication and DNA repair. The transient incorporation of H2A.Bbd may be due to the intrinsic instability of nucleosomes carrying this variant or a faster chromatin loading. This potentially leads to a disturbance of the existing chromatin structure, which may have effects on cell cycle regulation and DNA damage sensitivity. |
format | Online Article Text |
id | pubmed-4041467 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-40414672014-06-11 The histone variant H2A.Bbd is enriched at sites of DNA synthesis Sansoni, Viola Casas-Delucchi, Corella S. Rajan, Malini Schmidt, Andreas Bönisch, Clemens Thomae, Andreas W. Staege, Martin S. Hake, Sandra B. Cardoso, M. Cristina Imhof, Axel Nucleic Acids Res Genome Integrity, Repair and Replication Histone variants play an important role in shaping the mammalian epigenome and their aberrant expression is frequently observed in several types of cancer. However, the mechanisms that mediate their function and the composition of the variant-containing chromatin are still largely unknown. A proteomic interrogation of chromatin containing the different H2A variants macroH2A.1.2, H2A.Bbd and H2A revealed a strikingly different protein composition. Gene ontology analysis reveals a strong enrichment of splicing factors as well as components of the mammalian replisome in H2A.Bbd-containing chromatin. We find H2A.Bbd localizing transiently to sites of DNA synthesis during S-phase and during DNA repair. Cells that express H2A.Bbd have a shortened S-phase and are more susceptible to DNA damage, two phenotypes that are also observed in human Hodgkin's lymphoma cells that aberrantly express this variant. Based on our experiments we conclude that H2A.Bbd is targeted to newly synthesized DNA during replication and DNA repair. The transient incorporation of H2A.Bbd may be due to the intrinsic instability of nucleosomes carrying this variant or a faster chromatin loading. This potentially leads to a disturbance of the existing chromatin structure, which may have effects on cell cycle regulation and DNA damage sensitivity. Oxford University Press 2014-06-01 2014-04-20 /pmc/articles/PMC4041467/ /pubmed/24753410 http://dx.doi.org/10.1093/nar/gku303 Text en © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Genome Integrity, Repair and Replication Sansoni, Viola Casas-Delucchi, Corella S. Rajan, Malini Schmidt, Andreas Bönisch, Clemens Thomae, Andreas W. Staege, Martin S. Hake, Sandra B. Cardoso, M. Cristina Imhof, Axel The histone variant H2A.Bbd is enriched at sites of DNA synthesis |
title | The histone variant H2A.Bbd is enriched at sites of DNA synthesis |
title_full | The histone variant H2A.Bbd is enriched at sites of DNA synthesis |
title_fullStr | The histone variant H2A.Bbd is enriched at sites of DNA synthesis |
title_full_unstemmed | The histone variant H2A.Bbd is enriched at sites of DNA synthesis |
title_short | The histone variant H2A.Bbd is enriched at sites of DNA synthesis |
title_sort | histone variant h2a.bbd is enriched at sites of dna synthesis |
topic | Genome Integrity, Repair and Replication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041467/ https://www.ncbi.nlm.nih.gov/pubmed/24753410 http://dx.doi.org/10.1093/nar/gku303 |
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