时钟介导的BMAL1乙化控制着昼夜功能
Jun Hirayama1, Saurabh Sahar, Benedetto Grimaldi
1Department of Pharmacology, School of Medicine, University of California Irvine, Irvine 92697-4625, California, USA.
Nature
|December 14, 2007
概括
时钟蛋白对其伴侣BMAL1进行乙化,这是调节身体内部时钟的关键步骤. 这种乙化对于昼夜节律和基因表达的正常运作至关重要.
科学领域:
- 分子生物学分子生物学
- 时间生物学 时间生物学
- 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:
- 循环节律是由转录-翻译反循环调节的.
- 钟-BMAL1复合体激活基因表达,而加密染色体 (Crys) 抑制它.
- CLOCK 具有内在的 ヒ斯乙转移酶活性,影响基因表达.
研究的目的:
- 为了研究CLOCK的非素乙化活性.
- 确定BMAL1乙化在昼夜节律调节中的作用.
主要方法:
- 在小鼠肝脏中分析BMAL1乙化.
- 在BMAL1.1中保存的氨酸537残留物的突变.
- 细胞模型来评估昼夜节律性救援.
主要成果:
- CLOCK 在氨酸537上直接乙化BMAL1.
- BMAL1乙化是节奏性的,发生在小鼠肝脏中.
- 乙化BMAL1增强了CRY1的招募,促进了转录抑制.
- 一个K537R突变的BMAL1无法恢复昼夜节律.
结论:
- 时钟-BMAL1酶相互作用对于昼夜机械至关重要.
- 钟表的BMAL1乙化是一个关键的调节机制.
- 这种翻译后的修改微调了昼夜基因表达.
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