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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
Previous work from this laboratory has shown that expression of human cytomegalovirus (HCMV) immediate-early (IE) genes from the major immediate-early promoter (MIEP) is likely to be regulated by chromatin remodelling around the promoter affecting the acetylation state of core histone tails. The HCMV MIEP contains sequences that bind cellular transcription factors responsible for its negative regulation in undifferentiated, non-permissive cells. Ets-2 repressor factor (ERF) is one such factor that binds to such sequences and represses IE gene expression. Although it is not known how cellular transcription factors such as ERF mediate transcriptional repression of the MIEP, it is likely to involve differentiation-specific co-factors. In this study, the mechanism by which ERF represses HCMV IE gene expression was analysed. ERF physically interacts with the histone deacetylase, HDAC1, both in vitro and in vivo and this physical interaction between ERF and HDAC1 mediates repression of the MIEP. This suggests that silencing of viral IE gene expression, associated with histone deacetylation events around the MIEP, is mediated by differentiation-dependent cellular factors such as ERF, which specifically recruit chromatin remodellers to the MIEP in non-permissive cells.
Present address: Medical Research Council, Research Programme on AIDS in Uganda, c/o Uganda Virus Research Institute, PO Box 49, Entebbe, Uganda.
This article has been cited by other articles:
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  V. Lukashchuk, S. McFarlane, R. D. Everett, and C. M. Preston Human Cytomegalovirus Protein pp71 Displaces the Chromatin-Associated Factor ATRX from Nuclear Domain 10 at Early Stages of Infection J. Virol., December 15, 2008; 82(24): 12543 - 12554. [Abstract] [Full Text] [PDF]
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R. L. Sanders, C. L. Clark, C. S. Morello, and D. H. Spector Development of Cell Lines That Provide Tightly Controlled Temporal Translation of the Human Cytomegalovirus IE2 Proteins for Complementation and Functional Analyses of Growth-Impaired and Nonviable IE2 Mutant Viruses J. Virol., July 15, 2008; 82(14): 7059 - 7077. [Abstract] [Full Text] [PDF]
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 I. J. Groves and J. H. Sinclair Knockdown of hDaxx in normally non-permissive undifferentiated cells does not permit human cytomegalovirus immediate-early gene expression J. Gen. Virol., November 1, 2007; 88(11): 2935 - 2940. [Abstract] [Full Text] [PDF]
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 M. Verykokakis, C. Papadaki, E. Vorgia, L. Le Gallic, and G. Mavrothalassitis The RAS-dependent ERF Control of Cell Proliferation and Differentiation Is Mediated by c-Myc Repression J. Biol. Chem., October 12, 2007; 282(41): 30285 - 30294. [Abstract] [Full Text] [PDF]
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R. T. Saffert and R. F. Kalejta Human Cytomegalovirus Gene Expression Is Silenced by Daxx-Mediated Intrinsic Immune Defense in Model Latent Infections Established In Vitro J. Virol., September 1, 2007; 81(17): 9109 - 9120. [Abstract] [Full Text] [PDF]
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M. Shlapobersky, R. Sanders, C. Clark, and D. H. Spector Repression of HMGA2 Gene Expression by Human Cytomegalovirus Involves the IE2 86-Kilodalton Protein and Is Necessary for Efficient Viral Replication and Inhibition of Cyclin A Transcription. J. Virol., October 1, 2006; 80(20): 9951 - 9961. [Abstract] [Full Text] [PDF]
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M. Reeves, J. Murphy, R. Greaves, J. Fairley, A. Brehm, and J. Sinclair Autorepression of the Human Cytomegalovirus Major Immediate-Early Promoter/Enhancer at Late Times of Infection Is Mediated by the Recruitment of Chromatin Remodeling Enzymes by IE86. J. Virol., October 1, 2006; 80(20): 9998 - 10009. [Abstract] [Full Text] [PDF]
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J. Sinclair and P. Sissons Latency and reactivation of human cytomegalovirus J. Gen. Virol., July 1, 2006; 87(7): 1763 - 1779. [Abstract] [Full Text] [PDF]
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C. M. Preston and M. J. Nicholl Role of the cellular protein hDaxx in human cytomegalovirus immediate-early gene expression. J. Gen. Virol., May 1, 2006; 87(Pt 5): 1113 - 1121. [Abstract] [Full Text] [PDF]
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M. B. Reeves, P. J. Lehner, J. G. P. Sissons, and J. H. Sinclair An in vitro model for the regulation of human cytomegalovirus latency and reactivation in dendritic cells by chromatin remodelling J. Gen. Virol., November 1, 2005; 86(11): 2949 - 2954. [Abstract] [Full Text] [PDF]
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 M. B. Reeves, P. A. MacAry, P. J. Lehner, J. G. P. Sissons, and J. H. Sinclair Latency, chromatin remodeling, and reactivation of human cytomegalovirus in the dendritic cells of healthy carriers PNAS, March 15, 2005; 102(11): 4140 - 4145. [Abstract] [Full Text] [PDF]
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