cell20121109-13

来自美国斯克里普斯研究所细胞生物学系的Anton Maximov实验室发现HDAC4控制转录进程,这对于突触的可塑性和记忆很重要。

-2012年11月9日《细胞》


中文翻译


【题目】HDAC4控制转录进程

【译文】神经元活性影响一些回路发育和信息加工相关的基因。然而,这些进程的分子基础仍然知之甚少。我们发现HDAC4(一种组蛋白脱乙酰基酶)在细胞核和细胞质间穿梭,来控制转录过程,这对于突触可塑性和记忆有重要的作用。HDAC4的核输入和与其相关的染色质受到NMDA的负调节。在细胞核中,HADC4抑制编码中心突触组分的基因,从而影响突触的结合和强度。此外,我们发现HDAC4的一个截短形式(由一个与智力低下疾病相关的等位基因编码的)是一个具有增益功能的细胞核抑制子,这个截短蛋白可以在缺乏脱乙酰基酶区域的情况下抑制转录和突触的传送作用。携带有该突变的小鼠模拟了这个等位基因的作用,表现出神经传递、空间学习和记忆的缺陷。这些研究结果解释了一种经验依赖型可塑性的机制并且定义在大脑中HDAC4的生物学作用。

英文原稿


[Title]HDAC4 Governs a Transcriptional Program Essential for Synaptic Plasticity and Memory

[Authors]Richard Sando, Natalia Gounko, Simon Pieraut, Lujian Liao, John Yates, Anton Maximov

[Abstract]Neuronal activity influences genes involved in circuit development and information processing. However, the molecular basis of this process remains poorly understood. We found that HDAC4, a histone deacetylase that shuttles between the nucleus and cytoplasm, controls a transcriptional program essential for synaptic plasticity and memory. The nuclear import of HDAC4 and its association with chromatin is negatively regulated by NMDA receptors. In the nucleus, HDAC4 represses genes encoding constituents of central synapses, thereby affecting synaptic architecture and strength. Furthermore, we show that a truncated form of HDAC4 encoded by an allele associated with mental retardation is a gain-of-function nuclear repressor that abolishes transcription and synaptic transmission despite the loss of the deacetylase domain. Accordingly, mice carrying a mutant that mimics this allele exhibit deficits in neurotransmission, spatial learning, and memory. These studies elucidate a mechanism of experience-dependent plasticity and define the biological role of HDAC4 inthe brain.

原文地址

http://www.cell.com/abstract/S0092-8674(12)01236-6

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