|
DVID
|
5001663 |
|
VISID
|
TVIS20004165
|
|
Chromosome
|
chr1 |
|
GRCh38 Location
|
22054913, 22054971 |
|
Disease
|
Cervical carcinoma |
|
Sample
|
Cell line |
|
Virus Reference Genome
|
AF125673.1 |
|
Target Gene
|
CDC42 |
Literature Information
|
PubMed PMID
|
29364907
|
|
Published year
|
2018 |
|
Journal
|
PLoS genetics |
|
Title
|
HPV integration hijacks and multimerizes a cellular enhancer to generate a viral-cellular super-enhancer that drives high viral oncogene expression. |
|
Author
|
Warburton A,Redmond CJ,Dooley KE,Fu H,Gillison ML,Akagi K,Symer DE,Aladjem MI,McBride AA |
|
Evidence
|
Integration of human papillomavirus (HPV) genomes into cellular chromatin is common in HPV-associated cancers. Integration is random, and each site is unique depending on how and where the virus integrates. We recently showed that tandemly integrated HPV16 could result in the formation of a super-enhancer-like element that drives transcription of the viral oncogenes. Here, we characterize the chromatin landscape and genomic architecture of this integration locus to elucidate the mechanisms that promoted de novo super-enhancer formation. Using next-generation sequencing and molecular combing/fiber-FISH, we show that ~26 copies of HPV16 are integrated into an intergenic region of chromosome 2p23. This interspersed, co-amplified viral-host pattern is frequent in HPV-associated cancers and here we designate it as Type III integration. An abundant viral-cellular fusion transcript encoding the viral E6/E7 oncogenes is expressed from the integration locus and the chromatin encompassing both the viral enhancer and a region in the adjacent amplified cellular sequences is strongly enriched in the super-enhancer markers H3K27ac and Brd4. Thus, HPV16 integration generated a super-enhancer-like element composed of tandem interspersed copies of the viral upstream regulatory region and a cellular enhancer, to drive high levels of oncogene expression.
|
|
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HPV VIS Detail Information