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Title: | Epstein–Barr virus-mediated transformation of B cells induces global chromatin changes independent to the acquisition of proliferation |
Author: | Hernando, Henar Islam, Abul B. M. M. K. Rodríguez Ubreva, Javier Forné, Ignasi Ciudad, Laura Imhof, Axel Shannon-Lowe, Claire Ballestar Tarín, Esteban |
Keywords: | Herpesvirus Cèl·lules B Herpesviruses B cells |
Issue Date: | 1-Jan-2014 |
Publisher: | Oxford University Press |
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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1093/nar/gkt886 |
It is part of: | Nucleic Acids Research, 2014, vol. 42, num. 1, p. 249-263 |
URI: | http://hdl.handle.net/2445/126387 |
Related resource: | https://doi.org/10.1093/nar/gkt886 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) Publicacions de projectes de recerca finançats per la UE |
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