Epigenetic regulation of OAS2 shows disease-specific DNA methylation profiles at individual CpG sites.
Epigenetic regulation of OAS2 shows disease-specific DNA methylation profiles at individual CpG sites.
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DOI：
10.1038/srep32579
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发表时间：
2016-08-30
影响因子：
4.6
通讯作者：
Nylander K
中科院分区：
文献类型：
--
作者：
Gu X;Boldrup L;Coates PJ;Fahraeus R;Nylander E;Loizou C;Olofsson K;Norberg-Spaak L;Gärskog O;Nylander K
表观遗传修饰是生物过程的重要调节因子。在银屑病中发现了编码抗病毒蛋白的OAS 2（2′-5′-寡腺苷酸合成酶2）的DNA甲基化降低。为了进一步了解OAS 2的表观遗传调控，我们采用焦磷酸测序法检测了银屑病（n = 12）和头颈部两种常见鳞状细胞癌（SCC）亚型（舌（n = 12）和扁桃体（n = 11））中OAS 2 DNA 11个启动子和第一外显子CpG位点的甲基化状态。与相应的对照组相比，在银屑病中观察到普遍的低甲基化。在舌和扁桃体鳞状细胞癌中，仅在两个CpG位点发现低甲基化，这两个位点在银屑病中去甲基化程度最低。尽管针对甲基化/去甲基化的特定残基存在差异，但OAS 2表达在所有条件下均上调，并且在银屑病和舌SCC中观察到甲基化和表达之间的相关性。在63 bp的基因组区域内的四个连续定位的CpG位点处的独特甲基化状态揭示了一个精细整合的表观遗传程序，并表明对单个CpG的详细分析为特定疾病状态下的表观遗传调控机制提供了额外的信息。作为临床生物标志物的甲基化分析需要根据疾病特异性位点进行定制。
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.
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影响因子：
4.4
作者：
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