HISTONE DEACETYLASE 9 AS A NEGATIVE REGULATOR FOR CHOLINE ACETYLTRANSFERASE GENE IN NG108-15 NEURONAL CELLS
HISTONE DEACETYLASE 9 AS A NEGATIVE REGULATOR FOR CHOLINE ACETYLTRANSFERASE GENE IN NG108-15 NEURONAL CELLS
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DOI：
10.1016/j.neuroscience.2011.12.024
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发表时间：
2012-03-15
期刊：
影响因子：
3.3
通讯作者：
Yamamuro, Y.
中科院分区：
文献类型：
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作者：
Aizawa, S.;Teramoto, K.;Yamamuro, Y.
组蛋白去乙酰化酶（HDACs）的生物学功能，即通过去除组蛋白n端尾部的乙酰基来抑制基因表达，在包括大脑在内的个体组织的发育过程中，如细胞周期、分化和凋亡等许多生物学过程中发挥重要作用。我们之前在NG108-15神经细胞中作为胆碱能神经元的体外模型，展示了HDAC活性在调节胆碱乙酰转移酶（ChAT）基因表达中的可能作用，胆碱乙酰转移酶是胆碱能神经元的特异性标记物及其功能。本研究的目的是明确关键的hdac，并探讨hdac在NG108-15细胞ChAT基因调控中的重要作用。使用不同类型HDAC抑制剂的实验表明，Ila类HDAC实质性地参与了ChAT基因表达的调控。此外，在神经元分化过程中，hdac - 9酶在蛋白水平上显著降低，并与ChAT基因启动子区分离。此外，通过siRNA敲低HDAC9可增加未分化细胞中ChAT基因的表达。这些发现表明HDAC9在NG108-15神经元细胞中负责抑制ChAT基因的表达，从而在胆碱能分化中发挥重要作用。(c) 2012 ibro。Elsevier Ltd.出版。版权所有。
The biological function of histone deacetylases (HDACs), namely, repression of gene expression by removing an acetyl group from a histone N-terminal tail, plays an important role in numerous biological processes such as cell cycle, differentiation, and apoptosis in the development of individual tissues, including the brain. We previously showed the possible role of HDAC activity in the regulation of gene expression of choline acetyltransferase (ChAT), a specific marker for cholinergic neurons and their function, in NG108-15 neuronal cells as an in vitro model of cholinergic neurons. The objectives of the present study were to specify key HDACs and investigate the essential role of HDACs in ChAT gene regulation in NG108-15 cells. The experiments using different types of HDAC inhibitors indicated that class Ila HDACs substantially participate in the regulation of ChAT gene expression. In addition, HDAC9, a class Ila enzyme, was dramatically decreased at the protein levels, and dissociated from the promoter region of ChAT gene during neuronal differentiation. Furthermore, knockdown of HDAC9 by siRNA increased ChAT gene expression in undifferentiated cells. These findings demonstrate that HDAC9 is responsible for repressing ChAT gene expression in NG108-15 neuronal cells, and thus plays an important role in cholinergic differentiation. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.