Epstein–Barr virus-mediated transformation of B cells induces global chromatin changes independent to the acquisition of proliferation
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- dc.contributor.author Hernando, Henar
- dc.contributor.author Islam, Abul, 1978-
- dc.contributor.author Rodríguez Ubreva, Javier
- dc.contributor.author Forné, Ignasi
- dc.contributor.author Ciudad, Laura
- dc.contributor.author Imhof, Axel
- dc.contributor.author Shannon Lowe, Claire
- dc.contributor.author Ballestar, Esteban
- dc.date.accessioned 2024-01-23T07:15:54Z
- dc.date.available 2024-01-23T07:15:54Z
- dc.date.issued 2014
- dc.description.abstract Epstein–Barr virus (EBV) infects and transforms human primary B cells inducing indefinite proliferation. To investigate the potential participation of chromatin mechanisms during the EBV-mediated transformation of resting B cells we performed an analysis of global changes in histone modifications. We observed a remarkable decrease and redistribution of heterochromatin marks including H4K20me3, H3K27me3 and H3K9me3. Loss of H4K20me3 and H3K9me3 occurred at constitutive heterochromatin repeats. For H3K27me3 and H3K9me3, comparison of ChIP-seq data revealed a decrease in these marks in thousands of genes, including clusters of HOX and ZNF genes, respectively. Moreover, DNase-seq data comparison between resting and EBV-transformed B cells revealed increased endonuclease accessibility in thousands of genomic sites. We observed that both loss of H3K27me3 and increased accessibility are associated with transcriptional activation. These changes only occurred in B cells transformed with EBV and not in those stimulated to proliferate with CD40L/IL-4, despite their similarities in the cell pathways involved and proliferation rates. In fact, B cells infected with EBNA-2 deficient EBV, which have much lower proliferation rates, displayed similar decreases for heterochromatic histone marks. Our study describes a novel phenomenon related to transformation of B cells, and highlights its independence of the pure acquisition of proliferation.
- dc.description.sponsorship Spanish Ministry of Economy and Competitiveness (MINECO) [SAF2011-29635]; Fundación Ramón Areces [CIVP16A1834]; and Catalan Agency for Management of University and Research Grants (AGAUR) [2009SGR184]; Work in A.I.’s lab was funded by the European Union [EpiGeneSys 257082]. Funding for open access charge: MINECO [SAF2011-29635].
- dc.format.mimetype application/pdf
- dc.identifier.citation Hernando H, Islam ABMMK, Rodríguez-Ubreva J, Forné I, Ciudad L, Imhof A, et al. Epstein–Barr virus-mediated transformation of B cells induces global chromatin changes independent to the acquisition of proliferation. Nucleic Acids Research. 2014 Jan 1;42(1):249-63. DOI: 10.1093/nar/gkt886
- dc.identifier.doi http://dx.doi.org/10.1093/nar/gkt886
- dc.identifier.issn 0305-1048
- dc.identifier.uri http://hdl.handle.net/10230/58788
- dc.language.iso eng
- dc.publisher Oxford University Press
- dc.relation.ispartof Nucleic Acids Research. 2014 Jan 1;42(1):249-63
- dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/257082
- dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2011-29635
- dc.rights © The Author(s) 2013. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/3.0/
- dc.subject.other Virus d'Epstein-Barr
- dc.subject.other Cèl·lules B
- dc.subject.other Heterocromatina
- dc.title Epstein–Barr virus-mediated transformation of B cells induces global chromatin changes independent to the acquisition of proliferation
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion