The BZLF1 promoter of Epstein-Barr virus is controlled by E box-/HI-motif-binding factors during virus latency.
The BZLF1 open reading frame of Epstein-Barr virus (EBV) encodes an important transactivator of replication. During latency, transcription of this gene is switched off. HI motifs have been shown to cause negative regulation of the promoter. Using yeast one-hybrid assays, we isolated the E box-binding protein, E2-2, interacting with these motifs. Electrophoretic mobility shift assays demonstrated that E2-2 binds to HI alpha, HI beta and HI gamma, which contain E box consensus binding sites. Deletion of the HI-associated E boxes and overexpression of E2-2 in transfection assays revealed that these elements act as repressors in lymphoid cells. In contrast, in epithelial cells they contribute to the increased responsiveness of the promoter to transactivation by the BZLF1 protein. The data presented are in accord with an alternative and exclusive binding of different cell type- and differentiation-specific factors, such as E2-2, to the HI-associated E boxes in lymphoid and epithelial cells. This implies a role in cell type-specific virus replication.
Thomas
Cornelia
C
Institute for Medical Microbiology and Hygiene, University of Regensburg, Landshuter Strae 22, D-93047 Regensburg, Germany.
Dankesreiter
Arnd
A
Institute for Medical Microbiology and Hygiene, University of Regensburg, Landshuter Strae 22, D-93047 Regensburg, Germany.
Wolf
Hans
H
Institute for Medical Microbiology and Hygiene, University of Regensburg, Landshuter Strae 22, D-93047 Regensburg, Germany.
Schwarzmann
Fritz
F
Institute for Medical Microbiology and Hygiene, University of Regensburg, Landshuter Strae 22, D-93047 Regensburg, Germany.
D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D024721:E-Box Elements; D015967:Gene Expression Regulation, Viral; D018257:Helix-Loop-Helix Motifs; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology; D013045:Species Specificity; D051820:TCF Transcription Factors; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; D014158:Transcription, Genetic; D014764:Viral Proteins; D017735:Virus Latency
C063676:BZLF1 protein, Herpesvirus 4, Human; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; D014764:Viral Proteins