ZCCHC17 是阿尔茨海默病中突触基因表达的主要调节因子。
ZCCHC17 is a master regulator of synaptic gene expression in Alzheimer's disease.
机构信息
Department of Pathology and Cell Biology.
Taub Institute for Research on Alzheimer's Disease and the Aging Brain.
出版信息
Bioinformatics. 2018 Feb 1;34(3):367-371. doi: 10.1093/bioinformatics/btx608.
MOTIVATION
In an effort to better understand the molecular drivers of synaptic and neurophysiologic dysfunction in Alzheimer's disease (AD), we analyzed neuronal gene expression data from human AD brain tissue to identify master regulators of synaptic gene expression.
RESULTS
Master regulator analysis identifies ZCCHC17 as normally supporting the expression of a network of synaptic genes, and predicts that ZCCHC17 dysfunction in AD leads to lower expression of these genes. We demonstrate that ZCCHC17 is normally expressed in neurons and is reduced early in the course of AD pathology. We show that ZCCHC17 loss in rat neurons leads to lower expression of the majority of the predicted synaptic targets and that ZCCHC17 drives the expression of a similar gene network in humans and rats. These findings support a conserved function for ZCCHC17 between species and identify ZCCHC17 loss as an important early driver of lower synaptic gene expression in AD.
AVAILABILITY AND IMPLEMENTATION
Matlab and R scripts used in this paper are available at https://github.com/afteich/AD_ZCC.
CONTACT
SUPPLEMENTARY INFORMATION
Supplementary data are available at Bioinformatics online.
动机
为了更好地理解阿尔茨海默病（AD）中突触和神经生理功能障碍的分子驱动因素，我们分析了来自 AD 人脑组织的神经元基因表达数据，以确定突触基因表达的主要调控因子。
结果
主调控因子分析确定 ZCCHC17 通常支持突触基因表达网络的表达，并预测 AD 中 ZCCHC17 功能障碍导致这些基因表达降低。我们证明 ZCCHC17 在神经元中正常表达，并在 AD 病理过程的早期减少。我们表明，大鼠神经元中的 ZCCHC17 缺失导致大多数预测的突触靶基因的表达降低，并且 ZCCHC17 在人类和大鼠中驱动相似的基因网络表达。这些发现支持 ZCCHC17 在物种间的保守功能，并确定 ZCCHC17 缺失是 AD 中较低突触基因表达的重要早期驱动因素。
可用性和实施
本文中使用的 Matlab 和 R 脚本可在 https://github.com/afteich/AD_ZCC 获得。
联系方式
补充信息
补充数据可在生物信息学在线获得。
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