Nucleocytoplasmic translocation of HDAC9 regulates gene expression and dendritic growth in developing cortical neurons
Nucleocytoplasmic translocation of HDAC9 regulates gene expression and dendritic growth in developing cortical neurons
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DOI：
10.1111/j.1460-9568.2010.07218.x
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发表时间：
2010-05-01
影响因子：
3.4
通讯作者：
Yamamoto, Nobuhiko
中科院分区：
文献类型：
--
作者：
Sugo, Noriyuki;Oshiro, Hiroaki;Yamamoto, Nobuhiko
基因表达的转录调控被认为在活动依赖性神经元分化和回路形成中起关键作用。在这里，我们研究了组蛋白去乙酰化酶9（HDAC 9），它调节转录组蛋白修饰，在新皮层神经元的发展中的作用。HDAC 9从细胞核到细胞质的易位是由培养的小鼠皮层神经元自发放电活动的增加引起的。这种核质易位也观察到在体内出生后的发展。通过引入破坏核质易位的HDAC 9突变体进一步检查易位诱导的基因表达和细胞形态。c-fos，一个立即早期基因的表达，被抑制在muplatin转染的细胞，无论神经活动。此外，突变体的引入减少了树突状分支的总长度，而HDAC 9的敲除促进了树突状生长。这些发现表明，HDAC 9核质移位导致的染色质重塑调节发育中皮质神经元的活性依赖性基因表达和树突生长。
Transcriptional regulation of gene expression is thought to play a pivotal role in activity-dependent neuronal differentiation and circuit formation. Here, we investigated the role of histone deacetylase 9 (HDAC9), which regulates transcription by histone modification, in the development of neocortical neurons. The translocation of HDAC9 from nucleus to cytoplasm was induced by an increase of spontaneous firing activity in cultured mouse cortical neurons. This nucleocytoplasmic translocation was also observed in postnatal development in vivo. The translocation-induced gene expression and cellular morphology was further examined by introducing an HDAC9 mutant that disrupts the nucleocytoplasmic translocation. Expression of c-fos, an immediately-early gene, was suppressed in the mutant-transfected cells regardless of neural activity. Moreover, the introduction of the mutant decreased the total length of dendritic branches, whereas knockdown of HDAC9 promoted dendritic growth. These findings indicate that chromatin remodeling with nucleocytoplasmic translocation of HDAC9 regulates activity-dependent gene expression and dendritic growth in developing cortical neurons.