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The histone variant H2A.Bbd is enriched at sites of DNA synthesis.

Sansoni, Viola and Casas-Delucchi, Corella S. and Rajan, Malini and Schmidt, Andreas and Bönisch, Clemens and Thomae, Andreas W. and Staege, Martin S. and Hake, Sandra B. and Cardoso, M. Cristina and Imhof, Axel (2014):
The histone variant H2A.Bbd is enriched at sites of DNA synthesis.
In: Nucleic acids research, pp. 6405-20, 42, (10), ISSN 1362-4962, [Article]

Abstract

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.

Item Type: Article
Erschienen: 2014
Creators: Sansoni, Viola and Casas-Delucchi, Corella S. and Rajan, Malini and Schmidt, Andreas and Bönisch, Clemens and Thomae, Andreas W. and Staege, Martin S. and Hake, Sandra B. and Cardoso, M. Cristina and Imhof, Axel
Title: The histone variant H2A.Bbd is enriched at sites of DNA synthesis.
Language: English
Abstract:

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.

Journal or Publication Title: Nucleic acids research
Volume: 42
Number: 10
Divisions: 10 Department of Biology
10 Department of Biology > Cell Biology and Epigenetics
Date Deposited: 03 Sep 2014 08:34
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