McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Verdun, Quebec, Canada.
Int J Neuropsychopharmacol. 2012 Sep;15(8):1161-6. doi: 10.1017/S1461145711001520. Epub 2011 Oct 19.
Altered polyamine metabolism has been consistently observed as underlying the suicide process. We recently performed a global analysis of polyamine gene expression across the brains of suicide completers, and identified up-regulation of four genes, arginase II (ARG2), S-adenosylmethionine decarboxylase (AMD1), and antizymes 1 and 2 (OAZ1 and OAZ2), which play essential roles in polyamine biosynthesis. To determine if a shared epigenetic mechanism is involved in their overexpression in the prefrontal cortex, we measured promoter levels of tri-methyl modified histone-3-lysine-4 (H3K4me3), a marker of open chromatin, and assessed its association with suicide and gene expression. We identified increased H3K4me3 in the promoter region of OAZ1 in suicide, and found that H3K4me3 was correlated with the expression of OAZ1 and ARG2. Overall, our findings indicate that the H3K4me3 modification plays an important role in the regulation of polyamine biosynthesis, and that this mechanism may be involved in the neurobiology of suicide.
多胺代谢的改变一直被认为是自杀过程的基础。我们最近对自杀完成者大脑中的多胺基因表达进行了全面分析，发现了四种基因的上调，精氨酸酶 II（ARG2）、S-腺苷甲硫氨酸脱羧酶（AMD1）和抗酶 1 和 2（OAZ1 和 OAZ2），它们在多胺生物合成中发挥着重要作用。为了确定它们在前额叶皮层中过度表达是否涉及共同的表观遗传机制，我们测量了三甲基化修饰组蛋白-3-赖氨酸-4（H3K4me3）的启动子水平，这是开放染色质的标志物，并评估了其与自杀和基因表达的关联。我们在自杀中发现了 OAZ1 启动子区域中 H3K4me3 的增加，并且发现 H3K4me3 与 OAZ1 和 ARG2 的表达相关。总的来说，我们的研究结果表明，H3K4me3 修饰在多胺生物合成的调节中起着重要作用，并且该机制可能参与了自杀的神经生物学。
