Affiliation:
1. Comprehensive Transplant Center, Department of Surgery
2. Department of Microbiology and Immunology
3. Robert H. Lurie Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois
Abstract
ABSTRACT
Our previous studies showed that establishment of murine cytomegalovirus (MCMV) latency
in vivo
is associated with repression of immediate-early gene expression, deacetylation of histones bound to the major immediate-early promoter (MIEP), changes in patterns of methylation of histones, and recruitment of cellular repressors of transcription to the MIEP. Here, we have quantitatively analyzed the kinetics of changes in viral RNA expression, DNA copy number, and recruitment of repressors and activators of transcription to viral promoters during the course of infection. Our results show that changes in viral gene expression correlate with changes in recruitment of RNA polymerase and acetylated histones to viral promoters. Binding of the transcriptional repressors histone deacetylase type 2 (HDAC2), HDAC3, YY1, CBF-1/RBP-Jk, Daxx, and CIR to the MIEP and HDACs to other promoters showed a biphasic pattern: some binding was detectable prior to activation of viral gene expression, then decreased with the onset of transcription and increased again as repression of viral gene expression occurred. Potential binding sites for CBF-1/RBP-Jk and YY1 in the MIEP and for YY1 in the
M100
promoter (M100P) were identified by
in silico
analysis. While recruitment of HDACs was not promoter specific, binding of CBF-1/RBP-Jk and YY1 was restricted to promoters with their cognate sites. Our results suggest that sequences within viral promoters may contribute to establishment of latency through recruitment of transcriptional repressors to these genes. The observation that repressors are bound to the MIEP and other promoters immediately upon infection suggests that latency may be established in some cells very early in infection.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
Reference82 articles.
1. Disruption of PML Subnuclear Domains by the Acidic IE1 Protein of Human Cytomegalovirus Is Mediated through Interaction with PML and May Modulate a RING Finger-Dependent Cryptic Transactivator Function of PML
2. The major immediate-early proteins IE1 and IE2 of human cytomegalovirus colocalize with and disrupt PML-associated nuclear bodies at very early times in infected permissive cells
3. Austen, M., B. Luscher, and J. M. Luscher-Firzlaff. 1997. Characterization of the transcriptional regulator YY1. The bipartite transactivation domain is independent of interaction with the TATA box-binding protein, transcription factor IIB, TAFII55, or cAMP-responsive element-binding protein (CPB)-binding protein. J. Biol. Chem.272:1709-1717.
4. Bain, M., M. Reeves, and J. Sinclair. 2006. Regulation of human cytomegalovirus gene expression by chromatin remodeling, p. 167-183. In M. Reddehase (ed.), Cytomegaloviruses: molecular biology and immunology. Caister Academic Press, Norfolk, UK.
5. Lungs are a major organ site of cytomegalovirus latency and recurrence
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