Global CpG DNA Methylation Footprint in Kaposi's Sarcoma.
CpG methylation
KS
KSHV
Kaposi’s sarcoma
enhancer
gene expression
promoter
Journal
Frontiers in cellular and infection microbiology
ISSN: 2235-2988
Titre abrégé: Front Cell Infect Microbiol
Pays: Switzerland
ID NLM: 101585359
Informations de publication
Date de publication:
2021
2021
Historique:
received:
09
02
2021
accepted:
11
06
2021
entrez:
26
7
2021
pubmed:
27
7
2021
medline:
31
7
2021
Statut:
epublish
Résumé
Kaposi's sarcoma-associated herpesvirus (KSHV), also familiar as human herpesvirus 8 (HHV-8), is one of the well-known human cancer-causing viruses. KSHV was originally discovered by its association with Kaposi's sarcoma (KS), a common AIDS-related neoplasia. Additionally, KSHV is associated with two B-lymphocyte disorders; primary effusion lymphoma (PEL) and Multicentric Castlemans Disease (MCD). DNA methylation is an epigenetic modification that is essential for a properly functioning human genome through its roles in chromatin structure maintenance, chromosome stability and transcription regulation. Genomic studies show that expressed promoters tend to be un-methylated whereas methylated promoters tend to be inactive. We have previously revealed the global methylation footprint in PEL cells and found that many cellular gene promoters become differentially methylated and hence differentially expressed in KSHV chronically infected PEL cell lines. Here we present the cellular CpG DNA methylation footprint in KS, the most common malignancy associated with KSHV. We performed MethylationEPIC BeadChip to compare the global methylation status in normal skin compared to KS biopsies, and revealed dramatic global methylation alterations occurring in KS. Many of these changes were attributed to hyper-methylation of promoters and enhancers that regulate genes associated with abnormal skin morphology, a well-known hallmark of KS development. We observed six-fold increase in hypo-methylated CpGs between early stage of KS (plaque) and the more progressed stage (nodule). These observations suggest that hyper-methylation takes place early in KS while hypo-methylation is a later process that is more significant in nodule. Our findings add another layer to the understanding of the relationship between epigenetic changes caused by KSHV infection and tumorigenesis.
Identifiants
pubmed: 34307191
doi: 10.3389/fcimb.2021.666143
pmc: PMC8300563
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
666143Informations de copyright
Copyright © 2021 Journo, Ahuja, Dias-Polak, Eran, Bergman and Shamay.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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