Please use this identifier to cite or link to this item:
Title: The B cell transcription program mediates hypomethylation and overexpression of key genes in Epstein-Barr virus-associated proliferative conversion
Author: Hernando, Henar
Shannon-Lowe, Claire
Islam, Abul B. M. M. K.
Al-Shahrour, Fatima
Rodríguez Ubreva, Javier
Rodríguez Cortez, Virginia Carolina
Javierre, Biola M.
Mangas, Cristina
Fernández, Agustín F.
Parra Bola, Mª Isabel
Delecluse, Henri-Jacques
Esteller, Manel
López Granados, Eduardo
Fraga, Mario F.
López Bigas, Núria
Ballestar Tarín, Esteban
Keywords: Transcripció genètica
Genetic transcription
Issue Date: 15-Jan-2013
Publisher: BioMed Central
Abstract: Background: Epstein-Barr virus (EBV) infection is a well characterized etiopathogenic factor for a variety of immune-related conditions, including lymphomas, lymphoproliferative disorders and autoimmune diseases. EBV-mediated transformation of resting B cells to proliferating lymphoblastoid cells occurs in early stages of infection and is an excellent model for investigating the mechanisms associated with acquisition of unlimited growth. Results: We investigated the effects of experimental EBV infection of B cells on DNA methylation profiles by using high-throughput analysis. Remarkably, we observed hypomethylation of around 250 genes, but no hypermethylation. Hypomethylation did not occur at repetitive sequences, consistent with the absence of genomic instability in lymphoproliferative cells. Changes in methylation only occurred after cell divisions started, without the participation of the active demethylation machinery, and were concomitant with acquisition by B cells of the ability to proliferate. Gene Ontology analysis, expression profiling, and high-throughput analysis of the presence of transcription factor binding motifs and occupancy revealed that most genes undergoing hypomethylation are active and display the presence of NF-kappa B p65 and other B cell-specific transcription factors. Promoter hypomethylation was associated with upregulation of genes relevant for the phenotype of proliferating lymphoblasts. Interestingly, pharmacologically induced demethylation increased the efficiency of transformation of resting B cells to lymphoblastoid cells, consistent with productive cooperation between hypomethylation and lymphocyte proliferation. Conclusions: Our data provide novel clues on the role of the B cell transcription program leading to DNA methylation changes, which we find to be key to the EBV-associated conversion of resting B cells to proliferating lymphoblasts.
Note: Reproducció del document publicat a:
It is part of: Genome Biology, 2013, vol. 14, num. R3
Related resource:
ISSN: 1474-7596
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Files in This Item:
File Description SizeFormat 
662726.pdf1.76 MBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons