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While melatonin is best known as a master regulator of the circadian rhythm, previous studies also have revealed connections between circadian cycle disruption and genomic instability, including epigenetic changes in the pattern of DNA methylation. For example, melatonin secretion is associated with differential circadian gene methylation in night shift workers and the regulation of genomic methylation during embryonic development, and there is accumulating evidence that melatonin can modify DNA methylation. Since the latter one impacts cancer initiation, and also, non-malignant diseases development, and that targeting DNA methylation has become a novel intervention target in clinical therapy, this review discusses the potential role of melatonin as an under-investigated candidate epigenetic regulator, namely by modulating DNA methylation via changes in mRNA and the protein expression of DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) proteins. Furthermore, since melatonin may impact changes in the DNA methylation pattern, the authors of the review suggest its possible use in combination therapy with epigenetic drugs as a new anticancer strategy.<\/jats:p>","DOI":"10.3390\/antiox12061155","type":"journal-article","created":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T01:52:43Z","timestamp":1685065963000},"page":"1155","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Melatonin: A Potential Regulator of DNA Methylation"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7029-2657","authenticated-orcid":false,"given":"Kinga","family":"Linowiecka","sequence":"first","affiliation":[{"name":"Department of Human Biology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, Lwowska 1, 87-100 Toru\u0144, Poland"},{"name":"Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL 33125, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8963-3995","authenticated-orcid":false,"given":"Andrzej T.","family":"Slominski","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA"},{"name":"Pathology and Laboratory Medicine Service, VA Medical Center, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6763-4225","authenticated-orcid":false,"given":"Russel J.","family":"Reiter","sequence":"additional","affiliation":[{"name":"Department of Cell Systems and Anatomy, UT Health, Long School of Medicine, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"B\u00f6hm","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of M\u00fcnster, Von-Esmarch-Str. 58, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0500-2158","authenticated-orcid":false,"given":"Kerstin","family":"Steinbrink","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of M\u00fcnster, Von-Esmarch-Str. 58, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Paus","sequence":"additional","affiliation":[{"name":"Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL 33125, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1311-263X","authenticated-orcid":false,"given":"Konrad","family":"Kleszczy\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of M\u00fcnster, Von-Esmarch-Str. 58, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1210\/edrv-12-2-151","article-title":"Pineal Melatonin: Cell Biology of Its Synthesis and of Its Physiological Interactions","volume":"12","author":"Reiter","year":"1991","journal-title":"Endocr. 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