循环时钟调节器 Bmal1 门通过 Tet3 表观遗传在老鼠感官神经元中的轴突再生
Dalia Halawani1, Yiqun Wang1,2, Aarthi Ramakrishnan1
1Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Nature communications
|August 24, 2023
概括
昼夜时钟蛋白Bmal1通过限制表观遗传修饰来抑制背部根 (DRG) 神经元中的轴突再生. 准Bmal1促进神经修复,为外围神经损伤提供新的治疗途径.
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
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 背部根 (DRG) 神经元中的轴突再生对于外围神经受伤后的恢复至关重要.
- 基因调节机制是DRG轴突再生的基础,目前尚不完全理解.
- 循环时钟组件越来越多地被认为是超越日常节律的角色.
研究的目的:
- 研究昼夜转录因子Bmal1在DRG轴突再生中的作用.
- 阐明Bmal1影响神经元修复的分子机制.
- 探索针对Bmal1治疗增强轴突再生的潜力.
主要方法:
- 在小鼠DRG损伤后对差异化甲基化区域 (DhMRs) 的公正调查.
- 在DRG神经元中条件删除Bmal1.
- 在体外和体内神经元外生长试验.
- 转录基因分析.转录基因分析.
- 对表观遗传因子Tet3和5-基甲基细胞素 (5hmC) 修饰的分析.
主要成果:
- Bmal1结合基因被丰富在受损的DRG的DHMR中.
- 条件删除Bmal1促进了神经元在体外和体内生长.
- 发现Bmal1可以抑制轴突再生,部分是通过与Tet3.3的功能联系.
- Bmal1限制了Tet3表达和5hmC修饰,作为神经表观遗传反应的守门员.
- 确定了DRG神经元中Tet3和5hmC水平的表观遗传节奏,与轴突生长潜力的日间变化相关.
结论:
- Bmal1作为DRG神经元中轴突再生的负调节者.
- Bmal1-Tet3轴和5hmC修饰是控制神经再生的关键表观遗传机制.
- 准Bmal1是一个有希望的策略,可以增强轴突再生和神经损伤后的功能恢复.
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