Projects per year
Abstract
Host 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.
Original language | English |
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Pages (from-to) | 4770-4785 |
Number of pages | 16 |
Journal | Journal of virology |
Volume | 89 |
Issue number | 9 |
Early online date | 18 Feb 2015 |
DOIs | |
Publication status | Published - May 2015 |
Keywords
- Papillomavirus
- life cycle
- Gene expression
- CTCF
- Splicing
ASJC Scopus subject areas
- Cancer Research
- Biochemistry, Genetics and Molecular Biology (miscellaneous)
- Cell Biology
- Virology
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Dive into the research topics of 'CCCTC-Binding Factor Recruitment to the Early Region of the Human Papillomavirus Type 18 Genome Regulates Viral Oncogene Expression'. Together they form a unique fingerprint.Projects
- 2 Finished
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Understanding the function of CTCF recruitment to oncogenic HPV genomes in the complete HPV Life Cycle
1/10/13 → 30/09/17
Project: Research
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The Functional Role of ChIR1 in Genome Integrity and Papillomavirus Persistence
1/02/13 → 31/01/16
Project: Research Councils