%0 Journal Article
%T Methylation profiling of Epstein-Barr virus immediate-early gene promoters, BZLF1 and BRLF1 in tumors of epithelial, NK- and B-cell origins
%A Lili Li
%A Xianwei Su
%A Gigi Choi
%A Ya Cao
%A Richard F Ambinder
%A Qian Tao
%J BMC Cancer
%D 2012
%I BioMed Central
%R 10.1186/1471-2407-12-125
%X We evaluated the methylation profiles of Zp and Rp by methylation-specific PCR (MSP) and bisulfite genomic sequencing (BGS), as well as BZLF1 and BRLF1 expression by semiquantitative reverse transcription (RT)-PCR in tumors of epithelial, NK- and B-cell origins.We found that both Zp and Rp were hypermethylated in all studied EBV-positive cell lines and tumors of lymphoid (B- or NK cell) or epithelial origin, while unmethylated Zp and Rp alleles were detected in cell lines expressing BZLF1 and BRLF1. Following azacytidine treatment or combined with trichostatin A (TSA), the expression of BZLF1 and BRLF1 was restored along with concomitant promoter demethylation, which subsequently induced the reactivation of early lytic gene BHRF1 and late lytic gene BLLF1.Hypermethylation of Zp and Rp mediates the frequent silencing of BZLF1 and BRLF1 in EBV-associated tumors, which could be reactivated by demethylation agent and ultimately initiated the EBV lytic cascade.Epstein Barr virus (EBV) is a tumor virus associated with multiple human malignancies of lymphoid or epithelial origin, including Burkitt lymphoma (BL), Hodgkin disease (HD), nasopharyngeal carcinoma (NPC), gastric carcinoma (GsCa), nasal NK-lymphoma and posttransplant lymphoproliferative disease (PTLD), with more than 90% of adults infected in the world [1,2]. EBV has two types of infection in cells: latent or lytic. It persists in the human host as lifelong latent infection, which requires periodically reactivation of lytic genes and viral replication for maintaining its latency [3]. Two immediate-early (IE) proteins, BZLF1 (Zta) and BRLF1 (Rta), are essential to the switch from latent to lytic infection [4].Epigenetic regulation of EBV genome is a fundamental regulatory mechanism determining different types of EBV infections in its associated tumors [5-8]. Several latent or lytic genes, including EBV nuclear antigens (EBNA-2, 3A, 3B, 3 C), latent membrane protein 1 (LMP1), IE antigens (Zta, Rta) and lytic cycle
%U http://www.biomedcentral.com/1471-2407/12/125