Aberrant intracellular localization of H3k4me3 demonstrates an early epigenetic phenomenon in Alzheimer's disease.
Aberrant intracellular localization of H3k4me3 demonstrates an early epigenetic phenomenon in Alzheimer's disease.
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DOI：
10.1016/j.neurobiolaging.2015.08.017
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发表时间：
2015-12
影响因子：
4.2
通讯作者：
Coleman PD
中科院分区：
文献类型：
--
作者：
Mastroeni D;Delvaux E;Nolz J;Tan Y;Grover A;Oddo S;Coleman PD
我们以前曾报道在阿尔茨海默病（AD）的细胞核和细胞质之间的表观遗传分子的错误定位。我们已经将我们的发现扩展到包括组蛋白3三甲基化在赖氨酸4（H3k4me3）上的异常定位，这是一种与活跃转录基因以及那些准备转录的基因相关的表观遗传标记。这些发现提出了一个问题，即H3k4me3的异位定位在AD进展中的细胞生物学事件级联中的位置。因此，我们检查了H3k4me3的表达和细胞内位置作为Braak分期的函数，并且还与指示疾病状态的一系列tau标志物相关。这两条证据表明，H3k4me3的异位定位是在病程的早期。由于H3k4me3在突触基因表达中的已知作用，我们的数据表明，在AD病程早期突触缺陷中的表观遗传作用。
We have previously reported in Alzheimer’s disease (AD) the mislocalization of epigenetic molecules between the cell nucleus and the cytoplasm. We have extended our finding to include the aberrant localization of histone 3 trimethylation on lysine 4 (H3k4me3), an epigenetic mark associated with actively transcribing genes as well as those poised for transcription. These findings raise the question of where the ectopic localization of H3k4me3 fits within the cascade of cell biological events in the progression of AD. We, therefore, examined the expression and intracellular location of H3k4me3 as a function of Braak stage and also in relation to a series of tau markers that are indicative of disease state. Both lines of evidence showed that ectopic localization of H3k4me3 is early in the course of disease. Because of the known role of H3k4me3 in the expression of synaptic genes, our data suggest an epigenetic role in synaptic deficits early in the course of AD.
影响因子：
12.3
作者：
Bernstein BE;Kellis M
通讯作者：
Kellis M