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Genome-Wide Tiling Array Analysis of HPV-Induced Warts Reveals Aberrant Methylation of Protein-Coding and Non-Coding Regions.

ABSTRACT: The human papillomaviruses (HPV) are a group of double-stranded DNA viruses that exhibit an exclusive tropism for squamous epithelia. HPV can either be low- or high-risk depending on its ability to cause benign lesions or cancer, respectively. Unsurprisingly, the majority of epigenetic research has focused on the high-risk HPV types, neglecting the low-risk types in the process. Therefore, the main objective of this study is to better understand the epigenetics of wart formation by investigating the differences in methylation between HPV-induced cutaneous warts and normal skin. A number of clear and very significant differences in methylation patterns were found between cutaneous warts and normal skin. Around 55% of the top-ranking 100 differentially methylated genes in warts were protein coding, including the EXOC4, KCNU, RTN1, LGI1, IRF2, and NRG1 genes. Additionally, non-coding RNA genes, such as the AZIN1-AS1, LINC02008, and MGC27382 genes, constituted 11% of the top-ranking 100 differentially methylated genes. Warts exhibited a unique pattern of methylation that is a possible explanation for their transient nature. Since the genetics of cutaneous wart formation are not completely known, the findings of the present study could contribute to a better understanding of how HPV infection modulates host methylation to give rise to warts in the skin.

SUBMITTER: Al-Eitan LN

PROVIDER: S-EPMC7017144 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND: Non-coding RNAs (ncRNAs) play a crucial role in the intricate regulation of bacterial gene expression, allowing bacteria to quickly adapt to changing environments. In the past few years, a growing number of regulatory RNA elements have been predicted by computational methods, mostly in well-studied gamma-proteobacteria but lately in several alpha-proteobacteria as well. Here, we have compared an extensive compilation of these non-coding RNA predictions to intergenic expression data of a whole-genome high-resolution tiling array in the soil-dwelling alpha-proteobacterium Rhizobium etli. RESULTS: Expression of 89 candidate ncRNAs was detected, both on the chromosome and on the six megaplasmids encompassing the R. etli genome. Of these, 11 correspond to functionally well characterized ncRNAs, 12 were previously identified in other alpha-proteobacteria but are as yet uncharacterized and 66 were computationally predicted earlier but had not been experimentally identified and were therefore classified as novel ncRNAs. The latter comprise 17 putative sRNAs and 49 putative cis-regulatory ncRNAs. A selection of these candidate ncRNAs was validated by RT-qPCR, Northern blotting and 5' RACE, confirming the existence of 4 ncRNAs. Interestingly, individual transcript levels of numerous ncRNAs varied during free-living growth and during interaction with the eukaryotic host plant, pointing to possible ncRNA-dependent regulation of these specialized processes. CONCLUSIONS: Our data support the practical value of previous ncRNA prediction algorithms and significantly expand the list of candidate ncRNAs encoded in the intergenic regions of R. etli and, by extension, of alpha-proteobacteria. Moreover, we show high-resolution tiling arrays to be suitable tools for studying intergenic ncRNA transcription profiles across the genome. The differential expression levels of some of these ncRNAs may indicate a role in adaptation to changing environmental conditions.

Dataset Information

Genome-Wide Tiling Array Analysis of HPV-Induced Warts Reveals Aberrant Methylation of Protein-Coding and Non-Coding Regions.

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