title: Epigenetic regulation of OAS2 shows disease-specific DNA methylation profiles at individual CpG sites.
abstract: Epigenetic modifications are essential regulators of biological processes. Decreased DNA methylation of OAS2 (2'-5'-Oligoadenylate Synthetase 2), encoding an antiviral protein, has been seen in psoriasis. To provide further insight into the epigenetic regulation of OAS2, we performed pyrosequencing to detect OAS2 DNA methylation status at 11 promoter and first exon located CpG sites in psoriasis (n = 12) and two common subtypes of squamous cell carcinoma (SCC) of the head and neck: tongue (n = 12) and tonsillar (n = 11). Compared to corresponding controls, a general hypomethylation was seen in psoriasis. In tongue and tonsillar SCC, hypomethylation was found at only two CpG sites, the same two sites that were least demethylated in psoriasis. Despite differences in the specific residues targeted for methylation/demethylation, OAS2 expression was upregulated in all conditions and correlations between methylation and expression were seen in psoriasis and tongue SCC. Distinctive methylation status at four successively located CpG sites within a genomic area of 63 bp reveals a delicately integrated epigenetic program and indicates that detailed analysis of individual CpGs provides additional information into the mechanisms of epigenetic regulation in specific disease states. Methylation analyses as clinical biomarkers need to be tailored according to disease-specific sites.
authors: Department of Medical Biosciences/Pathology, Umeå University, Umeå, Sweden.
authors: Xiaolian
authors: X
authors: Gu
authors: Department of Medical Biosciences/Pathology, Umeå University, Umeå, Sweden.
authors: Linda
authors: L
authors: Boldrup
authors: RECAMO, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
authors: Philip J
authors: PJ
authors: Coates
authors: Department of Medical Biosciences/Pathology, Umeå University, Umeå, Sweden.|RECAMO, Masaryk Memorial Cancer Institute, Brno, Czech Republic.|Institut de Génétique Moléculaire, Université Paris 7, Hôpital St. Louis, Paris, France.
authors: Robin
authors: R
authors: Fahraeus
authors: Department of Public Health and Clinical Medicine/Dermatology and Venereology, Umeå University, Umeå, Sweden.
authors: Elisabet
authors: E
authors: Nylander
authors: Department of Clinical Sciences/ENT, Umeå University, Umeå, Sweden.
authors: Christos
authors: C
authors: Loizou
authors: Department of Clinical Sciences/ENT, Umeå University, Umeå, Sweden.
authors: Katarina
authors: K
authors: Olofsson
authors: Department of Clinical Sciences/ENT, Umeå University, Umeå, Sweden.
authors: Lena
authors: L
authors: Norberg-Spaak
authors: Department of Clinical Sciences/ENT, Umeå University, Umeå, Sweden.
authors: Ola
authors: O
authors: Gärskog
authors: Department of Medical Biosciences/Pathology, Umeå University, Umeå, Sweden.
authors: Karin
authors: K
authors: Nylander
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D011401:Promoter Regions, Genetic; D011565:Psoriasis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012189:Retrospective Studies; D014062:Tongue Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014067:Tonsillar Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: C000607948:OAS2 protein, human; D015088:2',5'-Oligoadenylate Synthetase