Nishioka Masaki, Shimada Takafumi, Bundo Miki, Ukai Wataru, Hashimoto Eri, Saito Toshikazu, Kano Yukiko, Sasaki Tsukasa, Kasai Kiyoto, Kato Tadafumi, Iwamoto Kazuya
Department of Molecular Psychiatry, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Japan.
Int J Dev Neurosci. 2013 Apr;31(2):89-95. doi: 10.1016/j.ijdevneu.2012.11.007. Epub 2012 Nov 23.
Gene expression of the alpha-1 subunit of the L-type voltage-gated calcium channel, CACNA1C, is known to be complexly regulated. Because CACNA1C is not only a crucial gene in normal brain function but also a promising candidate risk gene for psychiatric disorders such as bipolar disorder and schizophrenia, elucidating the molecular basis of transcriptional regulatory mechanism will be critically important. Here we examined DNA methylation status of CpG islands and a CpG island shore on mouse Cacna1c in neuronal and non-neuronal nuclei, which were separated with a fluorescent activated cell sorting technique. We found that neurons and non-neurons showed differential DNA methylation profile on a CpG island shore. This difference was evolutionarily conserved in human neuronal and non-neuronal nuclei in the prefrontal cortex, suggesting that DNA methylation status on the CpG island shore of Cacna1c may have an important role in transcript regulation.
已知L型电压门控钙通道α-1亚基（CACNA1C）的基因表达受到复杂调控。由于CACNA1C不仅是正常脑功能中的关键基因，还是双相情感障碍和精神分裂症等精神疾病的一个很有潜力的候选风险基因，因此阐明转录调控机制的分子基础至关重要。在这里，我们使用荧光激活细胞分选技术分离了小鼠Cacna1c在神经元和非神经元细胞核中的CpG岛和一个CpG岛岸的DNA甲基化状态。我们发现，神经元和非神经元在一个CpG岛岸上显示出不同的DNA甲基化谱。这种差异在人类前额叶皮质的神经元和非神经元细胞核中具有进化保守性，这表明Cacna1c的CpG岛岸的DNA甲基化状态可能在转录调控中发挥重要作用。
