Regional and Subcellular Distribution of HDAC4 in Mouse Brain
Regional and Subcellular Distribution of HDAC4 in Mouse Brain
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DOI：
10.1002/cne.22241
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发表时间：
2010-03-01
影响因子：
2.5
通讯作者：
Ouimet, Charles C.
中科院分区：
文献类型：
--
作者：
Darcy, Michael J.;Calvin, Kate;Ouimet, Charles C.
组蛋白去乙酰化酶（HDAC）是将基因表达的表观遗传控制与各种环境刺激联系起来的系统的一部分。一些HDAC，包括HDAC 4，响应于生理信号如钙信号在细胞质和细胞核之间穿梭。HDAC 4 mRNA在脑中富集，但HDAC 4的区域和亚细胞蛋白表达模式尚不清楚。在这里，我们发现HDAC 4在某些大脑区域的表达比其他区域更高。HDAC 4存在于大多数神经元的核周细胞质中，但其核定位是可变的。在某些区域，如齿状回，核表达是不可检测的，而在其他区域，一些神经元核含有HDAC 4免疫反应性，而其他则没有。在细胞质中，HDAC 4免疫反应性是点状的。这些斑点中的一些存在于树突棘中，其中最强的免疫反应性与突触后密度相关。这些数据表明，HDAC 4的区域和亚细胞分布是异质性的，并提高了HDAC 4作用于树突棘中的非组蛋白底物或穿梭于棘和核之间以协调突触活性与基因表达的可能性。J. Comp.神经元518：722-740，2010. (C)2009 Wiley-Liss，Inc
Histone deacetylases (HDACs) are part of a system that links epigenetic control of gene expression to a variety of environmental stimuli. Some HDACs, including HDAC4, shuttle between the cytoplasm and nucleus in response to physiological cues such as calcium signaling. HDAC4 mRNA is enriched in the brain, but the regional and subcellular protein expression pattern of HDAC4 is not known. Here we show that HDAC4 is more highly expressed in some brain regions than in others. HDAC4 is present in the perikaryial cytoplasm of most neurons but its nuclear localization is variable. In some areas, such as the dentate gyrus, nuclear expression is not detectable, whereas in other areas some neuronal nuclei contain HDAC4 immunoreactivity whereas others do not. In the cytoplasm, HDAC4 immunoreactivity is punctate. Some of these puncta are present in dendritic spines where the strongest immunoreactivity is associated with the postsynaptic density. These data demonstrate that the regional and subcellular distribution of HDAC4 is heterogeneous and raise the possibilities that HDAC4 acts on nonhistone substrates in dendritic spines or that it shuttles between spine and nucleus to coordinate synaptic activity with gene expression. J. Comp. Neurol. 518:722-740, 2010. (C) 2009 Wiley-Liss, Inc