Guide Epigenetics and Dermatology

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Epigenetics | Dermatology

QTY Add to cart. Submission Websites List. For the academic login, please select your organization on the next page. You will be redirected to verify your credentials. Corresponding Author Prof. Falk G. Background: The pathogenesis of hidradenitis suppurativa HS , with its complex inflammatory network, is still elusive. Imbalances in DNA methylation can lead to genome destabilization and have been assumed to play a role in inflammatory diseases. Objective: We conducted this study to investigate the global DNA methylation and hydroxymethylation status in lesional and perilesional HS skin compared to healthy controls.

Methods: Immunohistochemical analysis was performed for 5-methylcytosine 5-mC and 5-hydroxymethylcytosine 5-hmC in 30 lesional and 30 corresponding healthy-appearing perilesional HS tissue samples. We included 30 healthy subjects as an interindividual control group. In contrast to 5-hmC, 5-mC staining showed no significant changes between the 3 groups.

Univariate analysis revealed no significant association between patients' characteristics, disease severity, and the levels of 5-mC and 5-hmC.

Further studies are warranted to investigate the significance of DNA hydroxymethylation and the regulating enzymes in HS in order to advance our knowledge of the inflammatory network in this disease. The pathogenesis of hidradenitis suppurativa HS , which is a chronic inflammatory skin disease, is still elusive. Environmental factors such as smoking, bacterial colonization, and mechanical friction appear to be risk factors and may contribute to HS pathogenesis leading to inflamed nodules, abscesses, sinus tracts, fistulas, and scarring, most commonly in the inverse skin areas [ 1 , 2 , 3 , 4 ].

Therefore, genes predisposing to HS are under intense investigation.

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However, the reported mutations are found only in a minority of HS patients. Therefore, it must be assumed that further biological pathways may influence this skin condition which shows a wide variability in clinical phenotypes. Apart from variations in the genetic code, epigenetic modifications can also influence gene expression and may cause differences in phenotype and the immune system [ 11 , 12 ]. DNA methylation is one of the more studied epigenetic modifications and can be influenced by environmental factors [ 13 ].

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Several DNA methyltransferases DNMTs are responsible for de novo methylation by transferring a methyl group to the fifth position of the cytosine which results in methylation 5-methylcytosine, 5-mC [ 14 ]. Together with 5-formylcytosine and 5-carboxylcytosine, 5-hmC is an essential intermediate in the DNA demethylation process [ 15 ]. Imbalances in DNA methylation can lead to genome destabilization and deregulation of genes, and have been described to play a role in inflammatory diseases e. However, to the best of our knowledge, global DNA methylation and hydroxymethylation have not been studied in HS.

Therefore, we conducted this study to investigate the global methylation and hydroxymethylation status in HS patients and healthy controls. For further details, see the supplementary material for all online suppl. HS, hidradenitis suppurativa. With regard to levels of 5-mC, there was no significant difference between the 3 groups Fig.

The obtained mean H-scores for 5-mC and 5-hmC in the 3 groups are shown in detail in Table 1. Representative images of 5-mC immunostaining in 1 sample from healthy control b and perilesional c and lesional skin d of 1 representative hidradenitis suppurativa patient.

Representative images of 5-hmC immunostaining in 1 sample from healthy control b and perilesional c and lesional skin d of 1 representative hidradenitis suppurativa patient.

Next, we examined whether the content of 5-mC and 5-hmC in healthy controls and perilesional and lesional HS skin was influenced by patients' characteristics i. Univariate analysis revealed no significant association between the analyzed variables and the levels of 5-mC and 5-hmC Table 2. The imbalance between methylation and demethylation is well described in cancer, but it has also emerged as an important epigenetic modification in the development of inflammatory skin diseases [ 11 , 16 , 17 ].

However, to date, there are no reports concerning patients with HS. Our results showed no difference in the global DNA methylation, as measured by the level of 5-mC, in lesional and perilesional HS skin compared to healthy controls. Recently, emerging evidence has focused on the role of 5-hmC, a 5-mC oxidation derivate catalyzed by TET proteins. Our findings indicated significantly lower levels of 5-hmC in perilesional and lesional HS skin compared to healthy controls Fig.

However, there was no significant difference between lesional and perilesional HS skin regarding 5-hmC levels.

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Epigenetics and melanoma

Reportedly, 5-hmC homeostasis is largely influenced by 5-mC levels, which, in turn, would suggest that the loss of 5-hmC is accompanied by a loss or accumulation of its precursor 5-mC [ 21 ]. However, while we could show a significant reduction of the 5-hmC levels in lesional and perilesional HS skin compared to healthy controls, we did not observe any change of the global 5-mC levels. Thus, our data suggest that 5-hmC homeostasis is dynamic and an independent epigenetic marker. Accordingly, other studies showed that, beyond being a transient intermediate, 5-hmC is directly involved in the regulation of gene expression and transcription [ 22 , 23 , 24 ].

Decreased global levels of 5-hmC and unchanged 5-mC levels were observed in multiple cancers, including colon, prostate, and breast cancers [ 25 ]. In melanoma, loss of 5-hmC was observed compared to benign nevi, whereas the global levels of 5-mC showed no significant differences [ 22 ]. In contrast, in human osteoarthritic chondrocytes, 5-hmC levels were increased compared to normal chondrocytes, while the 5-mC levels did not differ significantly [ 26 ]. Aberrant 5-hydroxymethylation has also been observed in chronic inflammatory conditions.


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Studies showed that inflammatory cytokines regulate 5-hmC levels in an inflammatory microenvironment [ 26 , 27 ]. Therefore, our data indicate a link between the inflammatory microenvironment in HS and the epigenome [ 28 , 29 , 30 ].

Introduction

A study published in by Calabrese et al.