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

20Citations
Citations of this article
37Readers
Mendeley users who have this article in their library.

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. © The Author(s) 2013. Published by Oxford University Press.

Cite

CITATION STYLE

APA

Hernando, H., Islam, A. B. M. M. K., Rodríguez-Ubreva, J., Forné, I., Ciudad, L., Imhof, A., … Ballestar, E. (2014). Epstein-Barr virus-mediated transformation of B cells induces global chromatin changes independent to the acquisition of proliferation. Nucleic Acids Research, 42(1), 249–263. https://doi.org/10.1093/nar/gkt886

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free