餐时间改变了核O-GlcNAc蛋白质中的每日节奏,以调节肝脏基因表达
Xianhui Liu1,2,3, Yao D Cai2, Chunyan Hou4
1Cambridge-Suda Genomic Resource Center, The Fourth Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou 215123, Jiangsu, China.
bioRxiv : the preprint server for biology
|July 16, 2025
概括
肝脏中的节律性O-GlcNAcylation调节基因表达,并与酸化相互作用,影响肝脏的转录组. 改变食时间表会扰乱这些节奏,影响肝功能.
科学领域:
- 循环节律的代谢调节.
- 肝脏生物学中的翻译后修改.
- 对营养素敏感的信号通路.
背景情况:
- 肝脏的昼夜时钟和转录基因对食禁食周期作出反应.
- 营养敏感通路解释代谢信号以控制节律性肝脏生物学.
研究的目的:
- 研究O-GlcNAcylation在肝脏节律生物学代谢调节中的作用.
- 确定O-GlcNAcylation如何与酸化相互作用以影响肝脏转录组.
主要方法:
- 在夜间限制养 (NRF) 的小鼠中,无标签的全球O-GlcNAc蛋白质组.
- 使用双重质量标记质量谱法进行特定地点的O-GlcNAc分析.
- 在昼夜转录调节器中对O-GlcNAcylation-phosphorylation相互作用的分析.
主要成果:
- 在NRF小鼠中观察到的核蛋白O-GlcNAcylation的每日振荡.
- 在参与基因表达的蛋白质中发现了节律性O-GlcNAcylation.
- O-GlcNAcylation 调节了 CLOCK 蛋白质的稳定性和转录输出.
- 限日养 (DRF) 扰乱了O-GlcNAcylation节奏,一些部位显示反转的配置.
结论:
- 节律性O-GlcNAcylation通过与酸化的相互作用,可以机械调节每日肝脏转录组.
- 由于不适当的饮食时间而导致O-GlcNAcylation节律的破坏,有助于转录基因失调.
- 研究结果提供了关于肝脏昼夜生物学的代谢控制的见解.
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