Genomic profiling of the neuronal target genes of the plasticity-related transcription factor-Zif268
Genomic profiling of the neuronal target genes of the plasticity-related transcription factor-Zif268
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DOI：
10.1111/j.1471-4159.2005.03400.x
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发表时间：
2005-11-01
影响因子：
4.7
通讯作者：
Morris, BJ
中科院分区：
文献类型：
--
作者：
James, AB;Conway, AM;Morris, BJ
神经元可塑性的后期阶段总是依赖于基因转录。神经元中转录因子Zif 268（Egr-1）的诱导与许多形式的功能可塑性密切相关，但Zif 268调节的神经元靶基因尚未被表征。在用Zif 268转染神经元细胞系后，我们使用高密度微阵列鉴定了显示改变表达的基因。虽然一些基因先前已被确定与神经元可塑性的形式，大多数尚未与神经元可塑性或Zif 268行动。在Zif 268转染的PC 12神经元中，以及在Zif 268相关神经元可塑性的体外和体内模型中，证实了新靶基因的代表性样品的表达改变。特别是，氟哌啶醇给药后，在纹状体组织中观察到蛋白酶抑制剂胱抑素C和趋化因子Cxcl 10的表达改变。令人惊讶的是，一组鉴定的基因富含蛋白酶体和主要组织相容性复合体的成分。我们的研究结果表明，Zif 268诱导后这些基因的表达改变可能是CNS持久可塑性的关键组成部分。
The later phases of neuronal plasticity are invariably dependent on gene transcription. Induction of the transcription factor Zif268 (Egr-1) in neurones is closely associated with many forms of functional plasticity, yet the neuronal target genes modulated by Zif268 have not been characterized. After transfection of a neuronal cell line with Zif268 we identified genes that show altered expression using high density microarrays. Although some of the genes identified have previously been associated with forms of neuronal plasticity, the majority have not been linked with neuronal plasticity or Zif268 action. Altered expression of a representative sample of the novel target genes was confirmed in Zif268-transfected PC12 neurones, and in in vitro and in vivo models of Zif268-associated neuronal plasticity. In particular, altered expression of the protease inhibitor Cystatin C and the chemokine Cxcl10 was observed in striatal tissue after haloperidol administration. Surprisingly, the group of identified genes is enriched for components of the proteasome and the major histocompatibility complex. Our findings suggest that altered expression of these genes following Zif268 induction may be a key component of long lasting plasticity in the CNS.