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Cis-regulatory effect of HPV integration is constrained by host chromatin architecture in cervical cancers.
Singh, Anurag Kumar; Walavalkar, Kaivalya; Tavernari, Daniele; Ciriello, Giovanni; Notani, Dimple; Sabarinathan, Radhakrishnan.
Afiliación
  • Singh AK; National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bengaluru, India.
  • Walavalkar K; National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bengaluru, India.
  • Tavernari D; Department of Computational Biology, University of Lausanne (UNIL), Switzerland.
  • Ciriello G; Swiss Cancer Center Leman, Lausanne, Switzerland.
  • Notani D; Swiss Institute for Experimental Cancer Research (ISREC), EPFL, Lausanne, Switzerland.
  • Sabarinathan R; Department of Computational Biology, University of Lausanne (UNIL), Switzerland.
Mol Oncol ; 2023 Nov 27.
Article en En | MEDLINE | ID: mdl-38013620
Human papillomavirus (HPV) infections are the primary drivers of cervical cancers, and often HPV DNA gets integrated into the host genome. Although the oncogenic impact of HPV encoded genes is relatively well known, the cis-regulatory effect of integrated HPV DNA on host chromatin structure and gene regulation remains less understood. We investigated genome-wide patterns of HPV integrations and associated host gene expression changes in the context of host chromatin states and topologically associating domains (TADs). HPV integrations were significantly enriched in active chromatin regions and depleted in inactive ones. Interestingly, regardless of chromatin state, genomic regions flanking HPV integrations showed transcriptional upregulation. Nevertheless, upregulation (both local and long-range) was mostly confined to TADs with integration, but not affecting adjacent TADs. Few TADs showed recurrent integrations associated with overexpression of oncogenes within them (e.g. MYC, PVT1, TP63 and ERBB2) regardless of proximity. Hi-C and 4C-seq analyses in cervical cancer cell line (HeLa) demonstrated chromatin looping interactions between integrated HPV and MYC/PVT1 regions (~ 500 kb apart), leading to allele-specific overexpression. Based on these, we propose HPV integrations can trigger multimodal oncogenic activation to promote cancer progression.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mol Oncol Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2023 Tipo del documento: Article País de afiliación: India Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mol Oncol Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2023 Tipo del documento: Article País de afiliación: India Pais de publicación: Estados Unidos