scholarly journals Host-cell DNA methylation patterns during high-risk HPV-induced carcinogenesis reveal a heterogeneous nature of cervical pre-cancer

Epigenetics ◽  
2018 ◽  
Vol 13 (7) ◽  
pp. 769-778 ◽  
Author(s):  
Wina Verlaat ◽  
Robert W. Van Leeuwen ◽  
Putri W. Novianti ◽  
Ed Schuuring ◽  
Chris J. L. M. Meijer ◽  
...  
Keyword(s):  
Dna Methylation ◽  
High Risk ◽  
Host Cell ◽  
Heterogeneous Nature ◽  
High Risk Hpv ◽  
Methylation Patterns

scholarly journals DNA Methylation Patterns in Saliva of Tobacco users with High-Risk Oral Potentially Malignant Disorders

2021 ◽  
pp. 129-137
Author(s):  
Mimansha Patel ◽  
Madhuri Nitin Gawande ◽  
Minal Shashikant Chaudhary ◽  
Alka Harish Hande
Keyword(s):  
Dna Methylation ◽  
High Risk ◽  
Malignant Transformation ◽  
Promoter Methylation ◽  
Genomic Dna ◽  
Premalignant Lesions ◽  
Oral Potentially Malignant Disorders ◽  
Potentially Malignant Disorders ◽  
Potentially Malignant ◽  
Methylation Patterns

Background: “Oral Potentially Malignant Disorder (OPMD)” is a well-known symptom that, if untreated, can be carcinogenic. It includes leukoplakia, erythroplakia or erythroleukoplakia. One of the typical premalignant lesions of the oral cavity is “oral leukoplakias (OLs),” which frequently precedes “OSCCs.”OLs with dysplastic characteristics are considered to be at a higher risk of “malignant transformation.” So, early diagnosis of "oral squamous cell carcinomas (OSCCs)" is desperately required to enhance patient prognosis and quality of life (QOL).As a result, we examined the distinctive promoter methylation presence in high-risk OLs. Objectives: To detect, compare & correlate “DNA methylation” patterns in normal individuals, tobacco users without disease and tobacco users with the disease. Methodology: With the participants' full consent, 48 saliva samples were obtained and prepared. DNA isolation, restriction digestion of genomic DNA, extraction of restriction enzyme digested genomic DNA, Polymerase Chain Reaction (PCR), and Agarose Gel Electrophoresis (AGE) were all carried out. Expected results: This study will help us to assess the use of Saliva as an aid to identifying both high and low risk “Oral Potentially Malignant Disorders.” Conclusion: Peculiar promoter methylation of various genes was related to a high possibility of malignant transformation in OLs.

scholarly journals CCCTC-Binding Factor Recruitment to the Early Region of the Human Papillomavirus 18 Genome Regulates Viral Oncogene Expression

2015 ◽  
Vol 89 (9) ◽  
pp. 4770-4785 ◽  
Author(s):  
Christian Paris ◽  
Ieisha Pentland ◽  
Ian Groves ◽  
David C. Roberts ◽  
Simon J. Powis ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Risk ◽  
Host Cell ◽  
Viral Gene Expression ◽  
Early Gene ◽  
Ctcf Binding ◽  
Ctcf Binding Site ◽  
Viral Gene ◽  
Genome Wide ◽  
High Risk Hpv

ABSTRACTHost cell differentiation-dependent regulation of human papillomavirus (HPV) gene expression is required for productive infection. The host cell CCCTC-binding factor (CTCF) functions in genome-wide chromatin organization and gene regulation. We have identified a conserved CTCF binding site in the E2 open reading frame of high-risk HPV types. Using organotypic raft cultures of primary human keratinocytes containing high-risk HPV18 genomes, we show that CTCF recruitment to this conserved site regulates viral gene expression in differentiating epithelia. Mutation of the CTCF binding site increases the expression of the viral oncoproteins E6 and E7 and promotes host cell proliferation. Loss of CTCF binding results in a reduction of a specific alternatively spliced transcript expressed from the early gene region concomitant with an increase in the abundance of unspliced early transcripts. We conclude that high-risk HPV types have evolved to recruit CTCF to the early gene region to control the balance and complexity of splicing events that regulate viral oncoprotein expression.IMPORTANCEThe establishment and maintenance of HPV infection in undifferentiated basal cells of the squamous epithelia requires the activation of a subset of viral genes, termed early genes. The differentiation of infected cells initiates the expression of the late viral transcripts, allowing completion of the virus life cycle. This tightly controlled balance of differentiation-dependent viral gene expression allows the virus to stimulate cellular proliferation to support viral genome replication with minimal activation of the host immune response, promoting virus productivity. Alternative splicing of viral mRNAs further increases the complexity of viral gene expression. In this study, we show that the essential host cell protein CTCF, which functions in genome-wide chromatin organization and gene regulation, is recruited to the HPV genome and plays an essential role in the regulation of early viral gene expression and transcript processing. These data highlight a novel virus-host interaction important for HPV pathogenicity.

scholarly journals Role of genomic DNA methylation in detection of cytologic and histologic abnormalities in high risk HPV-infected women

PLoS ONE ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. e0210289 ◽  
Author(s):  
Wiyada Dankai ◽  
Surapan Khunamornpong ◽  
Sumalee Siriaunkgul ◽  
Aungsumalee Soongkhaw ◽  
Arphawan Janpanao ◽  
...  
Keyword(s):  
Dna Methylation ◽  
High Risk ◽  
Genomic Dna ◽  
High Risk Hpv

scholarly journals HPV16-Related Cervical Cancers and Precancers Have Increased Levels of Host Cell DNA Methylation in Women Living with HIV

2018 ◽  
Vol 19 (11) ◽  
pp. 3297 ◽  
Author(s):  
Wieke Kremer ◽  
Marjolein van Zummeren ◽  
Daniëlle Heideman ◽  
Birgit Lissenberg-Witte ◽  
Peter Snijders ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Host Cell ◽  
Invasive Cervical Cancer ◽  
Intraepithelial Neoplasia ◽  
Hpv Infection ◽  
Dna Hypermethylation ◽  
Cervical Disease ◽  
Hpv Types ◽  
High Risk Hpv

Data on human papillomavirus (HPV) type-specific cervical cancer risk in women living with human immunodeficiency virus (WLHIV) are needed to understand HPV–HIV interaction and to inform prevention programs for this population. We assessed high-risk HPV type-specific prevalence in cervical samples from 463 WLHIV from South Africa with different underlying, histologically confirmed stages of cervical disease. Secondly, we investigated DNA hypermethylation of host cell genes ASCL1, LHX8, and ST6GALNAC5, as markers of advanced cervical disease, in relation to type-specific HPV infection. Overall, HPV prevalence was 56% and positivity increased with severity of cervical disease: from 28.0% in cervical intraepithelial neoplasia (CIN) grade 1 or less (≤CIN1) to 100% in invasive cervical cancer (ICC). HPV16 was the most prevalent type, accounting for 9.9% of HPV-positive ≤CIN1, 14.3% of CIN2, 31.7% of CIN3, and 45.5% of ICC. HPV16 was significantly more associated with ICC and CIN3 than with ≤CIN1 (adjusted for age, ORMH 7.36 (95% CI 2.33–23.21) and 4.37 (95% CI 1.81–10.58), respectively), as opposed to non-16 high-risk HPV types. Methylation levels of ASCL1, LHX8, and ST6GALNAC5 in cervical scrapes of women with CIN3 or worse (CIN3+) associated with HPV16 were significantly higher compared with methylation levels in cervical scrapes of women with CIN3+ associated with non-16 high-risk HPV types (p-values 0.017, 0.019, and 0.026, respectively). When CIN3 and ICC were analysed separately, the same trend was observed, but the differences were not significant. Our results confirm the key role that HPV16 plays in uterine cervix carcinogenesis, and suggest that the evaluation of host cell gene methylation levels may monitor the progression of cervical neoplasms also in WLHIV.

Examination of the dynamics of global DNA methylation pattern establishment during spermatogenesiss

2007 ◽  
Vol 30 (4) ◽  
pp. 90
Author(s):  
Kirsten Niles ◽  
Sophie La Salle ◽  
Christopher Oakes ◽  
Jacquetta Trasler
Keyword(s):  
Dna Methylation ◽  
Germ Cell ◽  
Germ Cells ◽  
Epigenetic Modification ◽  
Methylation Pattern ◽  
Chromosome 9 ◽  
Specific Gene ◽  
Global Methylation ◽  
Dna Methylation Pattern ◽  
Methylation Patterns

Background: DNA methylation is an epigenetic modification involved in gene expression, genome stability, and genomic imprinting. In the male, methylation patterns are initially erased in primordial germ cells (PGCs) as they enter the gonadal ridge; methylation patterns are then acquired on CpG dinucleotides during gametogenesis. Correct pattern establishment is essential for normal spermatogenesis. To date, the characterization and timing of methylation pattern acquisition in PGCs has been described using a limited number of specific gene loci. This study aimed to describe DNA methylation pattern establishment dynamics during male gametogenesis through global methylation profiling techniques in a mouse model. Methods: Using a chromosome based approach, primers were designed for 24 regions spanning chromosome 9; intergenic, non-repeat, non-CpG island sequences were chosen for study based on previous evidence that these types of sequences are targets for testis-specific methylation events. The percent methylation was determined in each region by quantitative analysis of DNA methylation using real-time PCR (qAMP). The germ cell-specific pattern was determined by comparing methylation between spermatozoa and liver. To examine methylation in developing germ cells, spermatogonia from 2 day- and 6 day-old Oct4-GFP (green fluorescent protein) mice were isolated using fluorescence activated cell sorting. Results: As compared to liver, four loci were hypomethylated and five loci were hypermethylated in spermatozoa, supporting previous results indicating a unique methylation pattern in male germ cells. Only one region was hypomethylated and no regions were hypermethylated in day 6 spermatogonia as compared to mature spermatozoa, signifying that the bulk of DNA methylation is established prior to type A spermatogonia. The methylation in day 2 spermatogonia, germ cells that are just commencing mitosis, revealed differences of 15-20% compared to day 6 spermatogonia at five regions indicating that the most crucial phase of DNA methylation acquisition occurs prenatally. Conclusion: Together, these studies provide further evidence that germ cell methylation patterns differ from those in somatic tissues and suggest that much of methylation at intergenic sites is acquired during prenatal germ cell development. (Supported by CIHR)

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