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
Related in: MedlinePlus
Mentions: To assess the biological function of CTCF recruitment to the HPV18 genome in differentiating epithelium, WT and ΔCTCF HPV18 HFK lines were grown in organotypic raft culture. Formaldehyde-fixed rafts were paraffin embedded and sectioned. Sections were stained with hematoxylin and eosin to assess morphology (Fig. 6A). As previously described, the WT HPV18 genome-containing rafts were increased in thickness, and mitotic cells were visible in the lower and upper suprabasal layers of the rafts compared to rafts derived from HFKs that did not contain HPV18 genomes (13). This phenotype was enhanced in ΔCTCF HPV18 rafts, which were consistently thicker, indicating increased cellular proliferation. Alongside these experiments, viral genome amplification was assessed by chromogenic in situ hybridization (C-ISH). No consistent differences were observed in the number of cells with amplified HPV genomes between WT and ΔCTCF HPV18 rafts, demonstrating that CTCF recruitment has a minimal role in viral genome amplification (Fig. 6A and B).
Affiliation: University of St. Andrews, School of Medicine, St. Andrews, Fife, United Kingdom.