Mechanisms of specificity in neuronal activity-regulated gene transcription.
Mechanisms of specificity in neuronal activity-regulated gene transcription.
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DOI：
10.1016/j.pneurobio.2011.05.003
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发表时间：
2011-08
影响因子：
6.7
通讯作者：
West, Anne E.
中科院分区：
文献类型：
--
作者：
Lyons, Michelle R.;West, Anne E.
关键词：
大脑是一个适应性很强的器官，能够将感觉信息转化为神经元功能的变化。这种可塑性使行为能够适应环境，从而提供了重要的进化优势。神经元部分通过新基因产物的突触活动调节转录将环境刺激转化为其生理学的持久变化。自近 25 年前首次发现 Fos 转录的神经递质依赖性调节以来，大量研究丰富了我们对介导基因转录活动调节变化的分子途径的理解。这些发现表明，神经元活动可以参与广泛的信号传导途径和转录调节因子，以塑造刺激调节的基因转录的复杂程序。然而，神经元活动参与的转录途径的剪切范围提出了一个问题：如何实现转录反应性质的特异性，以编码对不同刺激的生理相关反应。在这里，我们总结了神经元活动调节转录的一般范式，同时重点关注在神经元基因转录的活动调节程序上赋予差异刺激、细胞类型和发育特异性的分子机制。此外，我们还预览了一些新技术，这些技术将促进我们未来对大脑中活动调节基因转录的机制和后果的理解。
The brain is a highly adaptable organ that is capable of converting sensory information into changes in neuronal function. This plasticity allows behavior to be accommodated to the environment, providing an important evolutionary advantage. Neurons convert environmental stimuli into long-lasting changes in their physiology in part through the synaptic activity-regulated transcription of new gene products. Since the neurotransmitter-dependent regulation of Fos transcription was first discovered nearly 25 years ago, a wealth of studies have enriched our understanding of the molecular pathways that mediate activity-regulated changes in gene transcription. These findings show that a broad range of signaling pathways and transcriptional regulators can be engaged by neuronal activity to sculpt complex programs of stimulus-regulated gene transcription. However, the shear scope of the transcriptional pathways engaged by neuronal activity raises the question of how specificity in the nature of the transcriptional response is achieved in order to encode physiologically relevant responses to divergent stimuli. Here we summarize the general paradigms by which neuronal activity regulates transcription while focusing on the molecular mechanisms that confer differential stimulus-, cell-type-, and developmental-specificity upon activity-regulated programs of neuronal gene transcription. In addition, we preview some of the new technologies that will advance our future understanding of the mechanisms and consequences of activity-regulated gene transcription in the brain.
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