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• W2113999862 abstract "In the present study, we used the human papillomavirus type 16 (HPV16)-positive cervical carcinoma cell line CaSki as a paradigmatic model to understand epigenetic silencing of viral multi-copy genomes. We show that most of the hypermethylated HPV16 copies are kept as ‘occluded’ chromatin that defines a condition where genes were refractory in their response to trans-acting transcription factors and to external reactivation efforts. This provides the first example that viral genomes are silenced by such a host cell mechanism, hitherto only known for endogenous genes to preserve a stable and robust phenotype. Moreover, considering an adaptive cross-talk between viral proteins and the epigenetic modification machinery, we demonstrate that particularly E2—but also ectopically delivered E6/E7—can induce significant de novo methylation within the enhancer and, to a less extent, within the promoter region. These data suggest that under certain physiological conditions, HPV can down-regulate its own gene expression, regardless of the presence of transcriptional activators. We propose that self-methylation of multi-copy HPV could be the first event prior to heterochromatin formation. These processes favour an ‘occluded’ chromatin conformation, finally being unresponsive to transcriptional activation. The shift from potentially competent heterochromatin towards an occluded state is basically irreversible, possibly using the same mechanism described for lineage differentiation. Along this line, it is tempting to speculate that virus–cell interaction is able to ‘sense’ viral copy number and down-regulates excess of gene activity in order to guarantee cell viability." @default.
• W2113999862 created "2016-06-24" @default.
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• W2113999862 date "2011-12-30" @default.
• W2113999862 modified "2023-09-26" @default.
• W2113999862 title "Silencing of multi-copy HPV16 by viral self-methylation and chromatin occlusion: a model for epigenetic virus–host interaction" @default.
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• W2113999862 doi "https://doi.org/10.1093/hmg/ddr604" @default.
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