环境昼夜干扰重新编程肝脏昼夜基因表达
Hao A Duong1,2, Kenkichi Baba1,2, Jason P DeBruyne1,2
1Department of Pharmacology and Toxicology, Morehouse School of Medicine, Atlanta GA 30310.
bioRxiv : the preprint server for biology
|September 11, 2023
概括
环境循环干扰 (ECD) 极大地改变了肝脏的循环基因表达,影响了新陈代谢. 大多数分子节奏都被ECD重写,即使在恢复后,效果也会持续下去.
科学领域:
- 时间生物学 时间生物学
- 分子生物学分子生物学
- 代谢学 代谢学 代谢学
背景情况:
- 昼夜基因表达对于生物钟的保存至关重要.
- 轮班工作和时差造成的环境环节干扰 (ECD) 影响了数百万人,但其分子影响尚不清楚.
- 了解ECD对肝脏昼夜节律的影响对公共健康至关重要.
研究的目的:
- 为了全面描述正常条件下的肝脏昼夜基因表达和ECD后.
- 调查昼夜节律变化的程度及其代谢后果.
主要方法:
- 在正常状态和ECD暴露状态下对肝脏昼夜基因表达的分析.
- 转录后和翻译后监管机制的特征.
- 评估转录组和蛋白质组的节律性变化以及相关的调节元素.
主要成果:
- 转录后和翻译后的过程显著塑造昼夜蛋白质组.
- ECD重写了64%的转录组,98%的全细胞蛋白质组和95%的核蛋白质组的节奏性.
- 这些变化与改变的 cis-regulatory 元素,RNA 处理和蛋白质贩运有关,损害了代谢调节.
结论:
- 脑电阻严重改变肝脏的分子节奏,影响基本的生物过程.
- 观察到的基因表达和蛋白质节律性的变化与改变的调节机制有关.
- 代谢调节障碍在ECD后仍然存在,突出显示了长期的健康后果.
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