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dc.contributor.authorParis, Christian
dc.contributor.authorPentland, Ieisha
dc.contributor.authorGroves, Ian
dc.contributor.authorRoberts, David C
dc.contributor.authorPowis, Simon J
dc.contributor.authorColeman, Nicholas
dc.contributor.authorRoberts, Sally
dc.contributor.authorParish, Joanna L
dc.identifier.citationParis , C , Pentland , I , Groves , I , Roberts , D C , Powis , S J , Coleman , N , Roberts , S & Parish , J L 2015 , ' CCCTC-binding factor recruitment to the early region of the human papillomavirus type 18 genome regulates viral oncogene expression ' , Journal of Virology , vol. 89 , no. 9 , pp. 4770-4785 .
dc.identifier.otherORCID: /0000-0003-4218-2984/work/60195317
dc.descriptionC.P. was supported by a Ph.D. studentshipfunded by the University of St. Andrews, School of Medicine. I.P. is supported by a Cancer Research UK (CRUK) Ph.D. studentship awarded to J.L.P. and S.R. I.G. and N.C. are supported by a CRUK Programme Award (13080) to N.C. J.L.P. is supported by a Royal Society University Research Fellowship (UF110010).en
dc.description.abstractHost cell differentiation-dependent regulation of human papillomavirus (HPV) gene expression is required for productive infection. The host cell CCCTC-binding factor (CTCF) functions in genome-wide chromatin organization and gene regulation. We have identified a conserved CTCF binding site in the E2 open reading frame of high-risk HPV types. Using organotypic raft cultures of primary human keratinocytes containing high-risk HPV18 genomes, we show that CTCF recruitment to this conserved site regulates viral gene expression in differentiating epithelia. Mutation of the CTCF binding site increases the expression of the viral oncoproteins E6 and E7, and promotes host cell proliferation. 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. We conclude that high-risk HPV types have evolved to recruit CTCF to the early gene region to control the balance and complexity of splicing events that regulate viral oncoprotein expression.
dc.relation.ispartofJournal of Virologyen
dc.subjectRC0254 Neoplasms. Tumors. Oncology (including Cancer)en
dc.subjectSDG 3 - Good Health and Well-beingen
dc.titleCCCTC-binding factor recruitment to the early region of the human papillomavirus type 18 genome regulates viral oncogene expressionen
dc.typeJournal articleen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.description.statusPeer revieweden

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