Epigenome-wide analysis of common warts reveals aberrant promoter methylation

Abstract

Epigenetic alteration of host DNA is a common occurrence in both low-and high-risk human papillomavirus (HPV) infection. Although changes in promoter methylation have been widely studied in HPV-associated cancers, they have not been the subject of much investigation in HPV-induced warts, which are a temporary manifestation of HPV infection. The present study sought to examine the differences in promoter methylation between warts and normal skin. To achieve this, DNA was extracted from 24 paired wart and normal skin samples and inputted into the Infinium MethylationEPIC BeadChip microarray. Differential methylation analysis revealed a clear pattern of hyper-and hypomethylation in warts compared to normal skin, and the most differentially methylated promoters were found within the EIF3EP2, CYSLTR1, C10orf99, KRT6B, LAMA4, and H3F3B genes as well as the C9orf30 pseudogene. Moreover, pathway analysis showed that the H3F3A, CDKN1A, and MAPK13 genes were the most common regulators among the most differentially methylated promoters. Since the tissue samples were excised from active warts, however, this differential methylation could either be a cellular response to HPV infection or an HPV-driven process to establish the wart and/or promote disease progression. Conclusively, it is apparent that HPV infection alters the methylation status of certain genes to possibly initiate the formation of a wart and maintain its presence.

Gene Expression Profile Analysis of Human Epidermal Keratinocytes Expressing Human Papillomavirus Type 8 E7

“…Further, the epigenetic regulators histone deacetylases (1 and 2) are overexpressed in oncoprotein E6/E7-expressing cells, and histone deacetylase inhibitors could be a therapeutic intervention for skin cancer induced by HPV [ 43 , 44 ]. An epigenome-wide analysis of HPV-driven common warts reveals that H3F3A, CDKN1A, and MAPK13 are the most differentially methylated genes [ 45 ]. Furthermore, HPV viral proteins can directly target histone methyltransferases for activity inhibition and modulate specific gene expression [ 39 ].…”

Identification of Differentially Methylated CpG Sites in Fibroblasts from Keloid Scars

“…Therefore, the identification of epigenetic targets could lead to therapeutic interventions. DNA methylation is an epigenetic gene regulatory mechanism that has been found to play a fundamental role in cancer [ 37 ], fibrotic disorders [ 15 , 38 , 39 ], cutaneous diseases [ 18 , 22 , 40 , 41 , 42 ], and wound healing [ 20 , 43 ]. DNA methylation is known to occur commonly at CpG islands and was traditionally linked to transcriptional silencing.…”