暂时特定的基因表达和染色体重塑程序调节了一个保存的Pdyn增强剂
Robert A Phillips1, Ethan Wan1, Jennifer J Tuscher1
1Department of Neurobiology, University of Alabama at Birmingham, Birmingham, United States.
eLife
|November 8, 2023
概括
直接早期基因 (IEGs) 通过在增强剂中重塑染色质来编排晚期基因反应,这对神经元可塑性和行为至关重要. 这项研究确定了一种调节prodynorphin (Pdyn) 表达的保存增强剂,这是神经精神疾病的潜在治疗标.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 遗传学 遗传学是一种遗传学.
背景情况:
- 神经元适应包括动态基因表达波,即时早期基因 (IEGs) 调节迟反应基因 (LRGs).
- 连接IEG与LRG的分子机制及其在染色质重塑中的作用尚不清楚.
研究的目的:
- 研究IEG和LRG在活动驱动神经元反应中的相互作用.
- 描述染色体可访问性变化,并确定参与晚期基因表达的调节元素.
主要方法:
- 在大鼠条状神经元中进行转录和染色质可访问性分析.
- 基于CRISPR的功能测试以验证增强剂活性.
- 对人类细胞中保存的调节元件的分析.
主要成果:
- 神经去极化诱导IEG表达1小时,LRG表达,包括神经和突触蛋白,在4小时.
- 显著的染色质重塑和成千上万的非编码部位的可访问性增加发生在4小时后,取决于IEG蛋白质合成.
- 一种调节prodynorphin (Pdyn) 转录的保存增强剂被确定并得到了功能验证.
结论:
- IEGs在增强剂的活性依赖性染色质重塑中发挥着关键作用.
- 保存的Pdyn增强剂对于Pdyn表达至关重要,并且可能是Pdyn相关神经精神疾病的治疗标.
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