CCCTC-binding factor recruitment to the early region of the human papillomavirus 18 genome regulates viral oncogene expression.
Bottom Line: Loss of CTCF binding results in a reduction of a specific alternatively spliced transcript expressed from the early gene region concomitant with an increase in the abundance of unspliced early transcripts.In this study, we show that the essential host cell protein CTCF, which functions in genome-wide chromatin organization and gene regulation, is recruited to the HPV genome and plays an essential role in the regulation of early viral gene expression and transcript processing.These data highlight a novel virus-host interaction important for HPV pathogenicity.
Affiliation: University of St. Andrews, School of Medicine, St. Andrews, Fife, United Kingdom.Show MeSH
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Mentions: We next used HPV16 and HPV18 genome-containing cells to ascertain whether CTCF associates with the viral genome in cells. W12 cells, derived from a low-grade cervical squamous epithelial lesion, contain ∼100 episomal HPV16 genome copies/cell (39, 40), and HPV18-transfected HFKs contain ∼200 episomal HPV18 copies/cell (see Fig. 5B). CTCF association with the HPV genomes was determined by ChIP followed by qPCR. In both HPV16 and HPV18 genome-containing cells grown in monolayer, we noted a significant enrichment of CTCF binding within the E2 ORF, coinciding with the CTCF binding site conserved in high-risk HPV types but not in low-risk types (Fig. 3). In contrast, we failed to detect CTCF binding to the late gene region in either HPV16 or HPV18 genome-containing model systems.
Affiliation: University of St. Andrews, School of Medicine, St. Andrews, Fife, United Kingdom.