The Epstein-Barr virus ZEBRA protein activates transcription from the early lytic F promoter by binding to a promoter-proximal AP-1-like site.
The ZEBRA protein encoded by the Epstein-Barr virus (EBV) genome activates a switch from the latent to the lytic gene expression programme of the virus. ZEBRA, a member of the basic leucine zipper family of DNA-binding proteins, is a transcriptional activator capable of inducing expression from several virus lytic cycle promoters by binding to activator protein 1 (AP-1)-like sites. The Epstein-Barr virus BamHI F promoter, Fp, was for some time believed to initiate EBNA1-specific transcription in EBV-transformed latent cells. More recent data, however, show that Fp is an early lytic promoter and that the dominant EBNA1 gene promoter in latent cells is Qp, located about 200 bp downstream of Fp. In the present investigation we confirm that Fp displays the characteristics of a lytic promoter. Fp is downregulated in latently EBV-infected cells, both in the endogenous virus genome and in reporter plasmids that carry Fp regulatory sequences upstream of position -136 and down to +10 relative to the Fp transcription start site (+1), and is activated on induction of the virus lytic cycle. We show that the repression of Fp in latent stages of infection can be abolished by ZEBRA, and demonstrate that ZEBRA activates Fp through a direct interaction with an AP-1-like site at position -52/-46 in the promoter-proximal Fp region.
Zetterberg
Henrik
H
Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Göteborg University, S-413 45 Gothenburg, Sweden1.
Jansson
Ann
A
Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Göteborg University, S-413 45 Gothenburg, Sweden1.
Rymo
Lars
L
Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Göteborg University, S-413 45 Gothenburg, Sweden1.
Chen
Fu
F
Microbiology and Tumor Biology Center, Karolinska Institute, S-171 77 Stockholm, Sweden2.
Karlsson
Ann
A
Microbiology and Tumor Biology Center, Karolinska Institute, S-171 77 Stockholm, Sweden2.
Klein
Georg
G
Microbiology and Tumor Biology Center, Karolinska Institute, S-171 77 Stockholm, Sweden2.
Brodin
Bertha
B
Cellular and Molecular Tumor Pathology, Cancer Centrum Karolinska, CCK R8:04, Karolinska Hospital, S-171 76 Stockholm, Sweden3.
D001402:B-Lymphocytes; D002460:Cell Line; D002461:Cell Line, Transformed; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015245:Deoxyribonuclease BamHI / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D017930:Genes, Reporter; D016679:Genome, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D010641:Phenotype; D010957:Plasmids; D011401:Promoter Regions, Genetic / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D014764:Viral Proteins; D014775:Virus Activation; D017735:Virus Latency
C063676:BZLF1 protein, Herpesvirus 4, Human; D004268:DNA-Binding Proteins; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D014764:Viral Proteins; D015245:Deoxyribonuclease BamHI