Abstract
All viruses target host cell factors for successful life cycle completion. Transcriptional control of DNA viruses by host cell factors is important in the temporal and spatial regulation of virus gene expression. Many of these factors are recruited to enhance virus gene expression and thereby increase virus production, but host cell factors can also restrict virus gene expression and productivity of infection. CCCTC binding factor (CTCF) is a host cell DNA binding protein important for the regulation of genomic chromatin boundaries, transcriptional control and enhancer element usage. CTCF also functions in RNA polymerase II regulation and in doing so can influence co-transcriptional splicing events. Several DNA viruses, including Kaposi’s sarcoma-associated herpesvirus (KSHV), Epstein-Barr virus (EBV) and human papillomavirus (HPV) utilize CTCF to control virus gene expression and many studies have highlighted a role for CTCF in the persistence of these diverse oncogenic viruses. CTCF can both enhance and repress virus gene expression and in some cases CTCF increases the complexity of alternatively spliced transcripts. This review article will discuss the function of CTCF in the life cycle of DNA viruses in the context of known host cell CTCF functions.
Highlights
CCCTC-binding factor (CTCF) is a ubiquitously expressed DNA binding protein that is highly conserved in bilaterian metazoans [1]
It is clear that CCCTC binding factor (CTCF) plays an integral role in virus genome organization and gene regulation, in both large and small DNA viruses
Studies have demonstrated that CTCF organizes viral genomes by creating boundaries between active and inactive chromatin and can regulate viral gene expression by altering RNA pol II recruitment and progression, and nucleosome positioning
Summary
CCCTC-binding factor (CTCF) is a ubiquitously expressed DNA binding protein that is highly conserved in bilaterian metazoans [1]. A more recent study has highlighted the potential for many more CTCF binding sites within the human genome (in the region of 300,000) whose occupancy depends on specific cell type and differentiation status [8]. The association of CTCF with the human genome is important for genomic organisation and the control of gene expression. Inhibition of CTCF binding by DNA methylation has been shown to alter gene-splicing events [10]. These important functions of CTCF in the control of host cell gene expression have been extensively reviewed elsewhere. We will focus this article on emerging evidence that CTCF is utilised by diverse DNA viruses to control viral gene expression, genome organisation, virus replication and persistence
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