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Rhythmic histone acetylation underlies transcription in the mammalian circadian clock

机译：节律性组蛋白乙酰化是哺乳动物昼夜节律时钟中转录的基础

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摘要

In the mouse circadian clock, a transcriptional feedback loop is at the centre of the clockwork mechanism. Clock and Bmall are essential transcription factors that drive the expression of three period genes (Per1-3) and two cryptochrome genes (Cry1 and Cry2). The Cry proteins feedback to inhibit Clock/Bmall-mediated transcription by a mechanism that does not alter Clock/Bmall binding to DNA. Here we show that transcriptional regulation of the core clock mechanism in mouse liver is accompanied by rhythms in H3 histone acetylation, and that H3 acetylation is a potential target of the inhibitory action of Cry. The promoter regions of the Per1, Per2 and Cry1 genes exhibit circadian rhythms in H3 acetylation and RNA polymerase Ⅱ binding that are synchronous with the corresponding steady-state messenger RNA rhythms. The histone acetyltransferase p300 precipitates together with Clock in vivo in a time-dependent manner. Moreover, the Cry proteins inhibit a p300-induced increase in Clock/Bmall-mediated transcription. The delayed timing of the Cry1 mRNA rhythm, relative to the Per rhythms, is due to the coordinated activities of Rev-Erba and Clock/Small, and defines a new mechanism for circadian phase control.
机译：在小鼠生物钟中，转录反馈环位于发条机制的中心。 Clock和Bmall是必需的转录因子，可驱动三个周期基因（Per1-3）和两个隐色基因（Cry1和Cry2）的表达。 Cry蛋白通过不改变Clock / Ball与DNA结合的机制来反馈抑制Clock / Ball介导的转录。在这里我们显示，小鼠肝脏中核心时钟机制的转录调节伴随着H3组蛋白乙酰化的节奏，并且H3乙酰化是Cry抑制作用的潜在目标。 Per1，Per2和Cry1基因的启动子区域在H3乙酰化和RNA聚合酶Ⅱ结合中表现出昼夜节律，与相应的稳态信使RNA节律同步。组蛋白乙酰转移酶p300与Clock在体内以时间依赖性方式沉淀。此外，Cry蛋白抑制p300诱导的Clock / Ball介导的转录增加。 Cry1 mRNA节律相对于Per节律的延迟时间是由于Rev-Erba和Clock / Small的协调活动，并定义了昼夜节律控制的新机制。

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  • 来源
    《Nature》 |2003年第6919期|p.177-182|共6页
  • 作者

    Jean-Pierre Etchegaray; Choogon Lee; Paul A. Wade; Steven M. Reppert;

  • 作者单位

    Department of Neurobiology, University of Massachusetts Medical School, LRB-728, 364 Plantation Street, Worcester, Massachusetts 01605, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 自然科学总论;
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