the b cell transcription program mediates hypomethylation and overexpression of key genes in epstein-barr virus-associated proliferative conversionb细胞转录程序调节hypomethylation关键基因的超表达eb病毒相关增殖的转换.pdf

Hernando et al. Genome Biology 2013, 14:R3 /2013/14/1/R3 RESEARCH Open Access The B cell transcription program mediates hypomethylation and overexpression of key genes in Epstein-Barr virus-associated proliferative conversion 1 2 3 4 1 Henar Hernando , Claire Shannon-Lowe , Abul B Islam , Fatima Al-Shahrour , Javier Rodríguez-Ubreva , 1 1 5 5 6 Virginia C Rodríguez-Cortez , Biola M Javierre , Cristina Mangas , Agustín F Fernández , Maribel Parra , 7 8 9 5,10 3 Henri-Jacques Delecluse , Manel Esteller , Eduardo López-Granados , Mario F Fraga , Nuria López-Bigas and Esteban Ballestar1* 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 st