title: Analysis of global methylation using a Zta-expressing nasopharyngeal carcinoma cell line.
abstract: EBV infects more than 90% of the human population and persists in most individuals as a latent infection where the viral genome is silenced by host-driven methylation. The lytic cycle is initiated when the viral protein Zta binds to methylated BRLF1 and BRRF1 promoters. Although studies reveal the role of Zta and methylation changes in the viral genome upon EBV infection to reactivation, whether Zta plays any role in alteration of methylation in the host genome remains unknown. Using an inducible model, we demonstrate that global DNA methylation, based on whole-genome 5-methylcytosine content, and regional DNA methylation in repetitive elements, imprinting genes and the X chromosome, remains unchanged in response to Zta expression. Expression of DNA methyltransferases was also unaffected by ectopically expressed Zta. Our data imply that alteration of host gene expression following EBV reactivation may reflect methylation-independent Zta-mediated gene activation and not epigenetic modification of the host genome.
authors.affiliation: Institute of Basic Medicine, College of Medicine, National Chung Kung University, Tainan, Taiwan.
authors.forename: Ying-Fan
authors.initials: YF
authors.lastname: Chen
authors.forename: Chao-Ling
authors.initials: CL
authors.lastname: Tung
authors.forename: Yao
authors.initials: Y
authors.lastname: Chang
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Hsiao
authors.forename: Lh-Jen
authors.initials: LJ
authors.lastname: Su
authors.forename: H Sunny
authors.initials: HS
authors.lastname: Sun
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism; D001483:Base Sequence; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000235:genetics*; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D020031:Epstein-Barr Virus Infections / Q000235:genetics* / Q000821:virology*; D016679:Genome, Viral / Q000235:genetics; D018392:Genomic Imprinting; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D049951:X Chromosome Inactivation / Q000235:genetics
chemical_list: C068382:BRLF1 protein, Human herpesvirus 4; C063676:BZLF1 protein, Herpesvirus 4, Human; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C035170:IGF2 protein, human; D017874:Immediate-Early Proteins; D015534:Trans-Activators; D007335:Insulin-Like Growth Factor II; D044503:5-Methylcytosine