ArticlePloS one2011
Differential methylation of the HPV 16 upstream regulatory region during epithelial differentiation and neoplastic transformation.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 103 citations in OpenAlex.
- Molecular insights and therapeutic innovations in low-risk human papillomavirus-associated cutaneous wart.Molecular biology reports · 2026Review
- Advances in understanding the mechanisms of the human papillomavirus oncoproteins.Biochemical Society transactions · 2025Review
- Identification of the Effects of 5-Azacytidine on Porcine Circovirus Type 2 Replication in Porcine Kidney Cells.Veterinary sciences · 2024Article
- Hypermethylated genome of a fish vertebrate iridovirus ISKNV plays important roles in viral infection.Communications biology · 2024Article
- The Hallmarks of Cervical Cancer: Molecular Mechanisms Induced by Human Papillomavirus.Biology · 2024Review
- Oncogenic Viruses and the Epigenome: How Viruses Hijack Epigenetic Mechanisms to Drive Cancer.International journal of molecular sciences · 2023Review
- Detection of Host Cell Gene/HPV DNA Methylation Markers: A Promising Triage Approach for Cervical Cancer.Frontiers in oncology · 2022Review
- Epigenetic and Transcriptomic Regulation Landscape in HPV+ Cancers: Biological and Clinical Implications.Frontiers in genetics · 2022Review
- The role of HPV-induced epigenetic changes in cervical carcinogenesis (Review).Biomedical reports · 2021Review
- Article
- Epigenetic Regulation of the Human Papillomavirus Life Cycle.Pathogens (Basel, Switzerland) · 2020Review
- Methylation of CpG 5962 in L1 of the human papillomavirus 16 genome as a potential predictive marker for viral persistence: A prospective large cohort study using cervical swab samples.Cancer medicine · 2020Article
- Detailed Characteristics of Tonsillar Tumors with Extrachromosomal or Integrated Form of Human Papillomavirus.Viruses · 2019Article
- Whole tissue cervical mapping of HPV infection: Molecular evidence for focal latent HPV infection in humans.Papillomavirus research (Amsterdam, Netherlands) · 2019Article
- Role of DNA methylation in HPV associated lesions.Papillomavirus research (Amsterdam, Netherlands) · 2019Review
- Comparison of methylation patterns of E6 gene promoter region in the low-risk and high-risk human papillomavirus.Iranian journal of microbiology · 2018Article
- Regulation of HPV transcription.Clinics (Sao Paulo, Brazil) · 2018Review
- HPV DNA methylation at the early promoter and E1/E2 integrity: A comparison between HPV16, HPV18 and HPV45 in cervical cancer.Papillomavirus research (Amsterdam, Netherlands) · 2018Article
- DNA Tumor Virus Regulation of Host DNA Methylation and Its Implications for Immune Evasion and Oncogenesis.Viruses · 2018Review
- Identification of reliable biomarkers of human papillomavirus 16 methylation in cervical lesions based on integration status using high-resolution melting analysis.Clinical epigenetics · 2018Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High risk human papillomaviruses are squamous epitheliotropic viruses that may cause cervical and other cancers. HPV replication depends on squamous epithelial differentiation. Transformation of HPV-infected cells goes along with substantial alteration of the viral gene expression profile and preferentially occurs at transformation zones usually at the uterine cervix. Methylation of the viral genome may affect regulatory features that control transcription and replication of the viral genome. Therefore, we analyzed the methylation pattern of the HPV16 upstream regulatory region (URR) during squamous epithelial differentiation and neoplastic transformation and analyzed how shifts in the HPV URR methylome may affect viral gene expression and replication. HPV 16 positive biopsy sections encompassing all stages of an HPV infection (latent, permissive and transforming) were micro-dissected and DNA was isolated from cell fractions representing the basal, intermediate, and superficial cell layers, each, as well as from transformed p16(INK4a)-positive cells. We observed fundamental changes in the methylation profile of transcription factor binding sites in the HPV16 upstream regulatory region linked to the squamous epithelial differentiation stage. Squamous epithelial transformation indicated by p16(INK4a) overexpression was associated with methylation of the distal E2 binding site 1 leading to hyper-activation of the HPV 16 URR. Adjacent normal but HPV 16-infected epithelial areas retained hyper-methylated HPV DNA suggesting that these viral genomes were inactivated. These data suggest that distinct shifts of the HPV 16 methylome are linked to differentiation dependent transcription and replication control and may trigger neoplastic transformation.
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