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J Gen Virol 84 (2003), 41-49; DOI 10.1099/vir.0.18633-0

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© 2003 Society for General Microbiology

Ets-2 Repressor Factor (ERF) mediates repression of the human cytomegalovirus major immediate-early promoter in undifferentiated non-permissive cells

Mark Bain, Marc Mendelson{dagger} and John Sinclair

Department of Medicine, University of Cambridge, PO Box 157, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK

Correspondence
John Sinclair
js{at}mole.bio.cam.ac.uk

The repression of human cytomegalovirus immediate-early (IE) lytic gene expression is crucial for the maintenance of the latent viral state. By using conditionally permissive cell lines, which provide a good model for the differentiation state-dependent repression of IE gene expression, we have identified several cellular factors that bind to the major immediate-early promoter (MIEP) and whose expression is down-regulated after differentiation to a permissive phenotype. Here we show that the cellular protein Ets-2 Repressor Factor (ERF) physically interacts with the MIEP and represses MIEP activity in undifferentiated non-permissive T2 embryonal carcinoma cells. This factor binds to the dyad element and the 21 bp repeats within the MIEP – regions known to be important for the negative regulation of MIEP activity. Finally, we show that following differentiation to a permissive phenotype ERF's repressive effects are severely abrogated.

{dagger}Present address: Infectious Diseases Clinical Research Unit, The Lung Institute, University of Cape Town, Cape Town, South Africa




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