DNA methylation status of SOX10 correlates with its downregulation and oligodendrocyte dysfunction in schizophrenia
DNA methylation status of SOX10 correlates with its downregulation and oligodendrocyte dysfunction in schizophrenia
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DOI：
10.1523/jneurosci.0766-05.2005
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发表时间：
2005-06-01
影响因子：
5.3
通讯作者：
Kato, T
中科院分区：
文献类型：
--
作者：
Iwamoto, K;Bundo, M;Kato, T
DNA微阵列研究揭示了精神分裂症中少突胶质细胞相关基因的下调，称为少突胶质细胞功能障碍。由于少突胶质细胞特异性转录因子调节少突胶质细胞的分化，编码它们的基因是精神分裂症少突胶质细胞功能障碍的主要候选者。我们发现，胞嘧啶-鸟嘌呤二核苷酸（CpG）岛的性别决定区Y盒基因10（S 0X 10），少突胶质细胞特异性转录因子，倾向于高度甲基化的精神分裂症患者的大脑中，与S 0X 10的表达减少。我们还发现S 0X 10的DNA甲基化状态也与精神分裂症中其他少突胶质细胞基因的表达相关。这可能是特定于S 0X 10，因为编码另一种少突胶质细胞特异性转录因子的OLIG 2的CpG岛在大脑中很少甲基化，并且编码少突胶质细胞结构蛋白的髓鞘相关少突胶质细胞碱性蛋白的甲基化状态不能解释它们的表达或其他少突胶质细胞基因的表达。因此，S 0X 10 CpG岛的DNA甲基化状态可能是精神分裂症少突胶质细胞功能障碍的表观遗传学标志。
Downregulation of oligodendrocyte-related genes, referred to as oligodendrocyte dysfunction, in schizophrenia has been revealed by DNA microarray studies. Because oligodendrocyte-specific transcription factors regulate the differentiation of oligodendrocytes, genes encoding them are prime candidates for oligodendrocyte dysfunction in schizophrenia. We found that the cytosine-guanine dinucleotide (CpG) island of sex-determining region Y-box containing gene 10 (S0X10), an oligodendrocyte-specific transcription factor, tended to be highly methylated in brains of patients with schizophrenia, correlated with reduced expression of S0X10. We also found that DNA methylation status of S0X10 also was associated with other oligodendrocyte gene expressions in schizophrenia. This may be specific to S0X10, because the CpG island of OLIG2, which encodes another oligodendrocyte-specific transcription factor, was rarely methylated in brains, and the methylation status of myelin-associated oligodendrocytic basic protein, which encodes structural protein in oligodendrocytes, did not account for their expressions or other oligodendrocyte gene expressions. Therefore, DNA methylation status of the S0X10 CpG island could be an epigenetic sign of oligodendrocyte dysfunction in schizophrenia.