Epstein-Barr virus-mediated transformation of B cells induces global chromatin changes independent to the acquisition of proliferation

Research output: Contribution to journalArticlepeer-review

Authors

  • Henar Hernando
  • Abul B M M K Islam
  • Javier Rodríguez-Ubreva
  • Ignasi Forné
  • Laura Ciudad
  • Axel Imhof
  • Esteban Ballestar

Colleges, School and Institutes

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.

Details

Original languageEnglish
Pages (from-to)249-63
Number of pages15
JournalNucleic Acids Research
Volume42
Issue number1
Early online date3 Oct 2013
Publication statusPublished - 1 Jan 2014

Keywords

  • B-Lymphocytes, Cell Proliferation, Herpesvirus 4, Human, Heterochromatin, Histones, Humans, Transformation, Genetic, Journal Article, Research Support, Non-U.S. Gov't