The Epstein-Barr virus transactivator Zta binds to its own promoter and is required for full promoter activity during anti-Ig and TGF-beta1 mediated reactivation.
Transcription of the immediate early gene BZLF1 is mediated initially through the activation of cellular transcription factors. Reporter-based studies have provided evidence that following this initial activation, the BZLF1 gene product Zta may be involved in an autoactivation loop through binding to its promoter Zp. In contrast, other reports have shown that transfection of a Zta expression vector in latently infected cells does not activate endogenous Zp. Using chromatin immunoprecipitation (ChIP) assays, we show here that Zta binds to endogenous Zp following induction of the lytic cycle by anti-Ig and TGF-beta1 and that binding occurs early enough to play a role in the activation of Zp. We have also generated a dominant-negative Zta and shown that it inhibits activation of endogenous Zp. These data support a two-step model for Zp activation during reactivation involving initial activation by cellular factors followed by an autoactivation step.
Tulane Cancer Center, Tulane Health Sciences Center, New Orleans, LA 70112, USA.
Qinyan
Q
Yin
Kendra
K
Jupiter
Erik K
EK
Flemington
D000906:Antibodies / Q000276:immunology*; D002460:Cell Line; D002843:Chromatin; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*; D014775:Virus Activation
D000906:Antibodies; C063676:BZLF1 protein, Herpesvirus 4, Human; D002843:Chromatin; D004268:DNA-Binding Proteins; D007136:Immunoglobulins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D014764:Viral Proteins