RTF1增强了CLK占用率和基因素甲基化在关键的昼夜钟心脏起器基因位点
Xu Liu1, Ya Huang1, Jiajia Fang1
1Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, Cambridge-Suda Genomic Resource Center, The Fourth Affiliated Hospital, Suzhou Medical College, Soochow University , Suzhou, China.
The Journal of cell biology
|November 4, 2025
概括
聚合酶相关因子1复合体 (Paf1C) 通过影响 CLOCK 蛋白活性来调节昼夜节律. 这项研究揭示了RTF1,一个Paf1C子单元,对于维持昼夜节律幅度和周期长度至关重要.
科学领域:
- 时间生物学 时间生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 循环时钟通过转录-翻译反循环来控制日常生理节奏.
- 时钟是关键的转录因子,但其对时钟基因的调节涉及同调节因子和基因组修饰.
研究的目的:
- 为了确定昼夜转录机械的新型调节者.
- 为了研究多索菲拉聚合酶相关因子1复合体 (Paf1C) 在昼夜时钟功能中的作用.
主要方法:
- RNA干扰 (RNAi) 用于在Drosophila心脏起神经元中击倒Paf1C子单元.
- 运动运动活动测试以评估昼夜周期和振幅.
- 西式涂抹和定量PCR测量蛋白质和基因表达.
- 染色体免疫沉 (ChIP) 用于分析蛋白占用率和基因组修饰.
- 同免疫沉以研究蛋白质相互作用.
- 在人类U2OS细胞中进行细胞培养实验.
主要成果:
- 在Drosophila心脏起神经元中,对Paf1C子单元,特别是RTF1的 Knockdown延长了昼夜移动周期并减轻了节律幅度.
- 通过降低每次转录,RTF1下调降低了PERIOD (PER) 蛋白水平.
- 每个人的过度表达拯救了由RTF1敲击造成的昼夜缺陷.
- RTF1与 CLOCK 物理相互作用,增强其在 per 和其他时钟基因促进者的占用率.
- SET1甲基转移酶与CLK和RTF1复合,在每小时促进者中增加H3K4me3水平.
- 人类RTF1与BMAL1/CLOCK相互作用,这表明哺乳动物的功能得到保护.
结论:
- RTF1是一种Drosophila昼夜节律的新型调节剂.
- RTF1通过增强 CLOCK 结合和促进 H3K4me3 修饰在目标促进体上来调节昼夜基因表达.
- 涉及RTF1,CLOCK和基因素修饰的机制在哺乳动物中可能存在.
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