Human endogenous retroviruses with transcriptional potential in the brain
Human endogenous retroviruses with transcriptional potential in the brain
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DOI：
10.1007/s10038-003-0081-8
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发表时间：
2003-11-01
影响因子：
3.5
通讯作者：
Jinno, Y
中科院分区：
文献类型：
--
作者：
Nakamura, A;Okazaki, Y;Jinno, Y
神经精神疾病的遗传学研究经常产生相互矛盾的结果，这可能部分是由于表观遗传修饰的参与。我们的目的是探讨DNA甲基化和人类内源性逆转录病毒（HERVs）在神经精神疾病中的可能意义。在本研究中，我们确定了两个HERV基因座，预计将保留在大脑中的转录活性。一个位于染色体1 q21-q22，另一个位于22 q12。有趣的是，这些区域分别与精神分裂症易感基因SCZD 9和SCZD 4重叠或包含在其中。特别是，22 q12上的HERV位于突触蛋白III基因下游4kb的相反方向。这些HERV基因座可以提供明确的目标，甲基化和表达分析，在死后的精神疾病，如精神分裂症患者的大脑。此外，我们证实了我们以前的发现，只有少数特定的HERV-K基因座被激活的高度同源基因座中的畸胎瘤细胞系。这些激活的基因座包括共同的所有畸胎瘤细胞系分析，并取决于其男性或女性的起源。
Genetic studies of neuropsychiatric disorders have often produced conflicting results, which might partly result from the involvement of epigenetic modifications. We intended to explore the possible implication of DNA methylation and human endogenous retroviruses (HERVs) in neuropsychiatric disorders. In the present study, we identified two HERV loci that are expected to retain the transcriptional activity in the brain. One was located on chromosome 1q21-q22 and the other on 22q12. Interestingly, these regions were overlapped with or included in those of schizophrenia-susceptible loci, SCZD9 and SCZD4, respectively. Particularly, the HERV on 22q12 was located in the opposite direction 4 kb downstream of the Synapsin III gene. These HERV loci could afford clear targets for methylation and expression analyses in postmortem brains of patients with psychiatric disorders such as schizophrenia. In addition, we confirmed our previous finding that only a few of particular HERV-K loci were activated among a number of highly homologous loci in teratocarcinoma cell lines. These activated loci included ones common to all teratocarcinoma cell lines analyzed and depending on their male or female origin.