Short- and long-range cis interactions between integrated HPV genomes and cellular chromatin dysregulate host gene expression in early cervical carcinogenesis.

Bibliographic Details
Title:	Short- and long-range cis interactions between integrated HPV genomes and cellular chromatin dysregulate host gene expression in early cervical carcinogenesis.
Authors:	Ian J Groves, Emma L A Drane, Marco Michalski, Jack M Monahan, Cinzia G Scarpini, Stephen P Smith, Giovanni Bussotti, Csilla Várnai, Stefan Schoenfelder, Peter Fraser, Anton J Enright, Nicholas Coleman
Source:	PLoS Pathogens, Vol 17, Iss 8, p e1009875 (2021)
Publisher Information:	Public Library of Science (PLoS), 2021.
Publication Year:	2021
Collection:	LCC:Immunologic diseases. Allergy LCC:Biology (General)
Subject Terms:	Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
More Details:	Development of cervical cancer is directly associated with integration of human papillomavirus (HPV) genomes into host chromosomes and subsequent modulation of HPV oncogene expression, which correlates with multi-layered epigenetic changes at the integrated HPV genomes. However, the process of integration itself and dysregulation of host gene expression at sites of integration in our model of HPV16 integrant clone natural selection has remained enigmatic. We now show, using a state-of-the-art 'HPV integrated site capture' (HISC) technique, that integration likely occurs through microhomology-mediated repair (MHMR) mechanisms via either a direct process, resulting in host sequence deletion (in our case, partially homozygously) or via a 'looping' mechanism by which flanking host regions become amplified. Furthermore, using our 'HPV16-specific Region Capture Hi-C' technique, we have determined that chromatin interactions between the integrated virus genome and host chromosomes, both at short- (500 kbp), appear to drive local host gene dysregulation through the disruption of host:host interactions within (but not exceeding) host structures known as topologically associating domains (TADs). This mechanism of HPV-induced host gene expression modulation indicates that integration of virus genomes near to or within a 'cancer-causing gene' is not essential to influence their expression and that these modifications to genome interactions could have a major role in selection of HPV integrants at the early stage of cervical neoplastic progression.
Document Type:	article
File Description:	electronic resource
Language:	English
ISSN:	1553-7366 1553-7374
Relation:	https://doaj.org/toc/1553-7366; https://doaj.org/toc/1553-7374
DOI:	10.1371/journal.ppat.1009875
Access URL:	https://doaj.org/article/c2ebaa15d87542a8b9191e3a5a74e587
Accession Number:	edsdoj.2ebaa15d87542a8b9191e3a5a74e587
Database:	Directory of Open Access Journals
Full text is not displayed to guests.	Login for full access.

More Details
ISSN:	15537366 15537374
DOI:	10.1371/journal.ppat.1009875
Published in:	PLoS Pathogens
Language:	English