Human papillomavirus integration transforms chromatin to drive oncogenesis.


Journal

Genome biology
ISSN: 1474-760X
Titre abrégé: Genome Biol
Pays: England
ID NLM: 100960660

Informations de publication

Date de publication:
27 06 2023
Historique:
received: 12 04 2022
accepted: 07 04 2023
medline: 28 6 2023
pubmed: 27 6 2023
entrez: 26 6 2023
Statut: epublish

Résumé

Human papillomavirus (HPV) drives almost all cervical cancers and up to 70% of head and neck cancers. Frequent integration into the host genome occurs predominantly in tumorigenic types of HPV. We hypothesize that changes in chromatin state at the location of integration can result in changes in gene expression that contribute to the tumorigenicity of HPV. We find that viral integration events often occur along with changes in chromatin state and expression of genes near the integration site. We investigate whether introduction of new transcription factor binding sites due to HPV integration could invoke these changes. Some regions within the HPV genome, particularly the position of a conserved CTCF binding site, show enriched chromatin accessibility signal. ChIP-seq reveals that the conserved CTCF binding site within the HPV genome binds CTCF in 4 HPV Our results suggest that introduction of a new CTCF binding site due to HPV integration reorganizes chromatin state and upregulates genes essential for tumor viability in some HPV

Sections du résumé

BACKGROUND
Human papillomavirus (HPV) drives almost all cervical cancers and up to 70% of head and neck cancers. Frequent integration into the host genome occurs predominantly in tumorigenic types of HPV. We hypothesize that changes in chromatin state at the location of integration can result in changes in gene expression that contribute to the tumorigenicity of HPV.
RESULTS
We find that viral integration events often occur along with changes in chromatin state and expression of genes near the integration site. We investigate whether introduction of new transcription factor binding sites due to HPV integration could invoke these changes. Some regions within the HPV genome, particularly the position of a conserved CTCF binding site, show enriched chromatin accessibility signal. ChIP-seq reveals that the conserved CTCF binding site within the HPV genome binds CTCF in 4 HPV
CONCLUSIONS
Our results suggest that introduction of a new CTCF binding site due to HPV integration reorganizes chromatin state and upregulates genes essential for tumor viability in some HPV

Identifiants

pubmed: 37365652
doi: 10.1186/s13059-023-02926-9
pii: 10.1186/s13059-023-02926-9
pmc: PMC10294493
doi:

Substances chimiques

Chromatin 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

142

Informations de copyright

© 2023. The Author(s).

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Auteurs

Mehran Karimzadeh (M)

Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Vector Institute for Artificial Intelligence, Toronto, ON, Canada.

Christopher Arlidge (C)

Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

Ariana Rostami (A)

Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

Mathieu Lupien (M)

Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada. mathieu.lupien@uhnresearch.ca.
Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. mathieu.lupien@uhnresearch.ca.

Scott V Bratman (SV)

Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada. scott.bratman@rmp.uhn.ca.
Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. scott.bratman@rmp.uhn.ca.

Michael M Hoffman (MM)

Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada. michael.hoffman@utoronto.ca.
Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. michael.hoffman@utoronto.ca.
Vector Institute for Artificial Intelligence, Toronto, ON, Canada. michael.hoffman@utoronto.ca.
Department of Computer Science, University of Toronto, Toronto, ON, Canada. michael.hoffman@utoronto.ca.

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