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DNA methylation and inflammatory skin diseases

  • Joshua S. Mervis
  • Jean S. McGeeEmail author
Review

Abstract

Epigenetics is the study of heritable changes in gene expression that do not originate from alternations in the DNA sequence. Epigenetic modifications include DNA methylation, histone modification, and gene silencing via the action of microRNAs. Epigenetic dysregulation has been implicated in many disease processes. In the field of dermatology, epigenetic regulation has been extensively explored as a pathologic mechanism in cutaneous T-cell lymphoma (CTCL), which has led to the successful development of epigenetic therapies for CTCL. In recent years, the potential role of epigenetic regulation in the pathogeneses of inflammatory skin diseases has gained greater appreciation. In particular, epigenetic changes in psoriasis and atopic dermatitis have been increasingly studied, with DNA methylation the most rigorously investigated to date. In this review, we provide an overview of DNA methylation in inflammatory skin diseases with an emphasis on psoriasis and atopic dermatitis.

Keywords

Epigenetics DNA methylation Inflammatory Skin diseases Psoriasis Atopic dermatitis 

Notes

Funding

The authors received no funding for this work.

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to disclose.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

Informed consent not required for this work.

References

  1. 1.
    Waddington CH (2012) The epigenotype. Int J Epidemiol 41(1):10–13PubMedCrossRefGoogle Scholar
  2. 2.
    Rodríguez-Paredes M, Esteller M (2011) Cancer epigenetics reaches mainstream oncology. Nat Med 17(3):330–339PubMedCrossRefGoogle Scholar
  3. 3.
    Berger SL, Kouzarides T, Shiekhattar R et al (2009) An operational definition of epigenetics. Genes Dev 23(7):781–783PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Feinberg AP, Koldobskiy MA, Göndör A (2016) Epigenetic modulators, modifiers and mediators in cancer aetiology and progression. Nat Rev Genet 17(5):284–299PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Dawson MA, Kouzarides T (2012) Cancer epigenetics: from mechanism to therapy. Cell 150(1):12–27PubMedCrossRefGoogle Scholar
  6. 6.
    Wu X, Zhang Y (2017) TET-mediated active DNA demethylation: mechanism, function and beyond. Nat Rev Genet 18(9):517–534PubMedCrossRefGoogle Scholar
  7. 7.
    Esteller M (2007) Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet 8(4):286–298PubMedCrossRefGoogle Scholar
  8. 8.
    Feinberg (2018) The key role of epigenetics in human disease. N Engl J Med 379(4):400–401PubMedCrossRefGoogle Scholar
  9. 9.
    Li Y, Sawalha AH, Lu Q (2009) Aberrant DNA methylation in skin diseases. J Dermatol Sci 54(3):143–149PubMedCrossRefGoogle Scholar
  10. 10.
    Shanmugam MK, Sethi G (2013) Role of epigenetics in inflammation-associated diseases. Subcell Biochem 61:627–657PubMedCrossRefGoogle Scholar
  11. 11.
    Jeltsch A, Jurkowska RZ (2014) New concepts in DNA methylation. Trends Biochem Sci 39(7):310–318PubMedCrossRefGoogle Scholar
  12. 12.
    Robertson KD (2005) DNA methylation and human disease. Nat Rev Genet 6(8):597–610PubMedCrossRefGoogle Scholar
  13. 13.
    Boehncke WH, Schön MP (2015) Psoriasis. Lancet 386:983–994PubMedCrossRefGoogle Scholar
  14. 14.
    Grozdev I, Korman N, Tsankov N (2014) Psoriasis as a systemic disease. Clin Dermatol 32(3):343–350PubMedCrossRefGoogle Scholar
  15. 15.
    Gladman DD, Antoni C, Mease P et al (2005) Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis 64(Suppl 2:ii1):4–7Google Scholar
  16. 16.
    Lu Q (2013) The critical importance of epigenetics in autoimmunity. J Autoimmun 41:1–5PubMedCrossRefGoogle Scholar
  17. 17.
    Wang Z, Long H, Chang C, Zhao M, Lu Q (2018) Crosstalk between metabolism and epigenetic modifications in autoimmune diseases: a comprehensive overview. Cell Mol Life Sci 75(18):3353–3369PubMedCrossRefGoogle Scholar
  18. 18.
    Zhao M, Lu Q (2018) The aberrant epigenetic modifications in the pathogenesis of psoriasis. J Investig Dermatol Symp Proc 19(2):S81–S82.PubMedCrossRefGoogle Scholar
  19. 19.
    Pollock RA, Abji F, Gladman DD (2017) Epigenetics of psoriatic disease: A systematic review and critical appraisal. J Autoimmun. 78:29–38PubMedCrossRefGoogle Scholar
  20. 20.
    Traupe H, van Gurp PJ, Happle R et al (1992) Psoriasis vulgaris, fetal growth, and genomic imprinting. Am J Med Genet 42(5):649–654PubMedCrossRefGoogle Scholar
  21. 21.
    Generali E, Ceribelli A, Stazi MA et al (2017) Lessons learned from twins in autoimmune and chronic inflammatory diseases. J Autoimmun 83:51–61PubMedCrossRefGoogle Scholar
  22. 22.
    Xiang Z, Yang Y, Chang C, Lu Q (2017) The epigenetic mechanism for discordance of autoimmunity in monozygotic twins. J Autoimmun 1(83):43–50CrossRefGoogle Scholar
  23. 23.
    Zhang P, Su Y, Chen H et al (2010) Abnormal DNA methylation in skin lesions and PBMCs of patients with psoriasis vulgaris. J Dermatol Sci 60(1):40–42PubMedCrossRefGoogle Scholar
  24. 24.
    Yooyongsatit S, Ruchusatsawat K, Noppakun N et al (2015) Patterns and functional roles of LINE-1 and Alu methylation in the keratinocyte from patients with psoriasis vulgaris. J Hum Genet 60(7):349–355PubMedCrossRefGoogle Scholar
  25. 25.
    Murata Y, Bundo M, Ueda J et al (2017) DNA methylation and hydroxymethylation analyses of the active LINE-1 subfamilies in mice. Sci Rep 7(1):13624PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Roberson ED, Liu Y, Ryan C et al (2012) A subset of methylated CpG sites differentiate psoriatic from normal skin. J Invest Dermatol. 132(3):583–592PubMedCrossRefGoogle Scholar
  27. 27.
    Verma D, Ekman AK, Bivik Eding C et al (2018) Genome-wide DNA methylation profiling identifies differential methylation in uninvolved psoriatic epidermis. J Invest Dermatol 138(5):1088–1093PubMedCrossRefGoogle Scholar
  28. 28.
    Zhang P, Zhao M, Liang G et al (2013) Whole-genome DNA methylation in skin lesions from patients with psoriasis vulgaris. J Autoimmun 41:17–24PubMedCrossRefGoogle Scholar
  29. 29.
    Zhou F, Wang W, Shen C et al (2016) Epigenome-wide association analysis identified nine skin DNA methylation loci for psoriasis. J Invest Dermatol 136(4):779–787PubMedCrossRefGoogle Scholar
  30. 30.
    Tang L, Cheng Y, Zhu C et al (2018) Integrative methylome and transcriptome analysis to dissect key biological pathways for psoriasis in Chinese Han population. J Dermatol Sci 91(3):285–291PubMedCrossRefGoogle Scholar
  31. 31.
    Chen M, Chen ZQ, Cui PG et al (2008) The methylation pattern of p16INK4a gene promoter in psoriatic epidermis and its clinical significance. Br J Dermatol 158(5):987–993PubMedCrossRefGoogle Scholar
  32. 32.
    Chen M, Wang Y, Yao X et al (2016) Hypermethylation of HLA-C may be an epigenetic marker in psoriasis. J Dermatol Sci. 83(1):10–16PubMedCrossRefGoogle Scholar
  33. 33.
    Chandra A, Senapati S, Roy S et al (2018) Epigenome-wide DNA methylation regulates cardinal pathological features of psoriasis. Clin Epigenetics 10(1):108PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Gervin K, Vigeland MD, Mattingsdal M et al (2012) DNA methylation and gene expression changes in monozygotic twins discordant for psoriasis: identification of epigenetically dysregulated genes. PLoS Genet 8(1):e1002454PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Han J, Park SG, Bae JB et al (2012) The characteristics of genome-wide DNA methylation in naïve CD4+ T cells of patients with psoriasis or atopic dermatitis. Biochem Biophys Res Commun 422(1):157–163PubMedCrossRefGoogle Scholar
  36. 36.
    Park GT, Han J, Park SG et al (2014) DNA methylation analysis of CD4+ T cells in patients with psoriasis. Arch Dermatol Res. 306(3):259–268PubMedCrossRefGoogle Scholar
  37. 37.
    Gu X, Nylander E, Coates PJ et al (2015) Correlation between reversal of DNA methylation and clinical symptoms in psoriatic epidermis following narrow-band UVB phototherapy. J Invest Dermatol 135(8):2077–2083PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Bieber T (2008) Atopic dermatitis. N Engl J Med 358(14):1483–1494PubMedCrossRefGoogle Scholar
  39. 39.
    Liang Y, Chang C, Lu Q (2016) The genetics and epigenetics of atopic dermatitis—filaggrin and other polymorphisms. Clin Rev Allergy Immunol 51(3):315–328PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Lockett GA, Soto-Ramírez N, Ray MA et al (2016) Association of season of birth with DNA methylation and allergic disease. Allergy 71(9):1314–1324PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Wang IJ, Chen SL, Lu TP et al (2013) Prenatal smoke exposure, DNA methylation, and childhood atopic dermatitis. Clin Exp Allergy 43(5):535–543PubMedCrossRefGoogle Scholar
  42. 42.
    Nguyen CM, Liao W (2015) Genomic imprinting in psoriasis and atopic dermatitis: a review. J Dermatol Sci 80(2):89–93PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Nakamura T, Sekigawa I, Ogasawara H et al (2006) Expression of DNMT-1 in patients with atopic dermatitis. Arch Dermatol Res 298(5):253–256PubMedCrossRefGoogle Scholar
  44. 44.
    Novak N, Bieber T, Leung DY (2003) Immune mechanisms leading to atopic dermatitis. J Allergy Clin Immunol. 112(6 Suppl):S128–S139PubMedCrossRefGoogle Scholar
  45. 45.
    Luo Y, Zhou B, Zhao M et al (2014) Promoter demethylation contributes to TSLP overexpression in skin lesions of patients with atopic dermatitis. Clin Exp Dermatol 39(1):48–53PubMedCrossRefGoogle Scholar
  46. 46.
    Ziyab AH, Karmaus W, Holloway JW et al (2013) DNA methylation of the filaggrin gene adds to the risk of eczema associated with loss-of-function variants. J Eur Acad Dermatol Venereol 27(3):e420–e423PubMedCrossRefGoogle Scholar
  47. 47.
    Rodríguez E, Baurecht H, Wahn AF et al (2014) An integrated epigenetic and transcriptomic analysis reveals distinct tissue-specific patterns of DNA methylation associated with atopic dermatitis. J Invest Dermatol 134(7):1873–1883PubMedCrossRefGoogle Scholar
  48. 48.
    Leoni C, Montagner S, Rinaldi A et al (2017) DNMT3a restrains mast cell inflammatory responses. Proc Natl Acad Sci USA 114(8):E1490–E1499PubMedCrossRefGoogle Scholar
  49. 49.
    Leoni C, Montagner S, Deho' L et al (2015) Reduced DNA methylation and hydroxymethylation in patients with systemic mastocytosis. Eur J Haematol 95(6):566–575PubMedCrossRefGoogle Scholar
  50. 50.
    Shukla A, Sehgal M, Singh TR (2015) Hydroxymethylation and its potential implication in DNA repair system: a review and future perspectives. Gene 564(2):109–118PubMedCrossRefGoogle Scholar
  51. 51.
    Hessam S, Sand M, Lang K et al (2017) Altered global 5-hydroxymethylation status in hidradenitis suppurativa: support for an epigenetic background. Dermatology 233(2–3):129–135PubMedCrossRefGoogle Scholar
  52. 52.
    Cruz AF, de Resende RG, de Lacerda JCT et al (2018) DNA methylation patterns of genes related to immune response in the different clinical forms of oral lichen planus. J Oral Pathol Med. 47(1):91–95PubMedCrossRefGoogle Scholar
  53. 53.
    Mervis JS, McGee JS (2019) Epigenetic therapy and dermatologic disease: moving beyond CTCL. J Dermatolog Treat 30(1):68–73PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of DermatologyBoston University School of MedicineBostonUSA

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