Methylation profiling of Epstein-Barr virus immediate-early gene promoters, BZLF1 and BRLF1in tumors of epithelial, NK- and B-cell originsReportar como inadecuado




Methylation profiling of Epstein-Barr virus immediate-early gene promoters, BZLF1 and BRLF1in tumors of epithelial, NK- and B-cell origins - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Cancer

, 12:125

First Online: 29 March 2012Received: 18 October 2011Accepted: 29 March 2012DOI: 10.1186-1471-2407-12-125

Cite this article as: Li, L., Su, X., Choi, G.C.G. et al. BMC Cancer 2012 12: 125. doi:10.1186-1471-2407-12-125

Abstract

BackgroundEpstein-Barr virus EBV establishes its latency in EBV-associated malignancies, accompanied by occasionally reactivated lytic cycle. Promoter CpG methylation of EBV genome plays an essential role in maintaining viral latency. Two immediate-early IE genes, BZLF1 and BRLF1, induce the switch from latent to lytic infection. Studies of methylation-dependent binding of BZLF1 and BRLF1 to EBV promoters have been well reported, but little is known about the methylation status of BZLF1 and BRLF1 promoters Zp and Rp in tumor samples.

MethodsWe 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.

ResultsWe 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.

ConclusionsHypermethylation 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.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-12-125 contains supplementary material, which is available to authorized users.

Download fulltext PDF



Autor: Lili Li - Xianwei Su - Gigi Ching Gee Choi - Ya Cao - Richard F Ambinder - Qian Tao

Fuente: https://link.springer.com/







Documentos relacionados