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Reciprocal Regulation between the Circadian Clock and Hypoxia Signaling at the Genome Level in Mammals

机译：哺乳动物基因组水平昼夜节点与缺氧信号之间的互核调节

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摘要

Circadian regulation is critically important in maintaining metabolic and physiological homeostasis. However, little is known about the possible influence of the clock on physiological abnormalities occurring under pathological conditions. Here, we report the discovery that hypoxia, a condition that causes catastrophic bodily damage, is gated by the circadian clock in vivo. Hypoxia signals conversely regulate the clock by slowing the circadian cycle and dampening the amplitude of oscillations in a dose-dependent manner. ChIP-seq analyses of hypoxia-inducible factor HIF1A and the core clock component BMAL1 revealed crosstalk between hypoxia and the clock at the genome level. Further, severe consequences caused by acute hypoxia, such as those that occur with heart attacks, were correlated with defects in circadian rhythms. We propose that the clock plays functions in fine-tuning hypoxic responses under pathophysiological conditions. We argue that the clock can, and likely should, be exploited therapeutically to reduce the severity of fatal hypoxia-related diseases.
机译：昼夜节约法规在维持代谢和生理稳态方面是至关重要的。然而，关于在病理条件下发生的生理异常的时钟可能的影响很少。在这里，我们报告发现缺氧，导致灾难性身体损坏的条件被昼夜节日在体内浇注。缺氧信号通过减慢昼夜循环并以剂量依赖的方式抑制振荡振荡的振荡来调节时钟。缺氧诱导因子HIF1A和核心时钟组分BMA1的CHIP-SEQ分析揭示了基因组水平缺氧与时钟之间的串扰。此外，由急性缺氧引起的严重后果，例如心脏病发作发生的那些，与昼夜节律的缺陷相关。我们提出了在病理生理病症下进行微调缺氧响应的功能。我们认为时钟可以，并且可能应该被剥削治疗，以降低致命缺氧相关疾病的严重程度。

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  • 来源
    《Cell metabolism》 |2017年第1期|共13页
  • 作者

    Wu Yaling; Tang Dingbin; Liu Na; Xiong Wei; Huang Huanwei; Li Yang; Ma Zhixiong; Zhao Haijiao; Chen Peihao; Qi Xiangbing; Zhang Eric Erquan;

  • 作者单位

    Beijing Normal Univ Coll Life Sci Beijing 100875 Peoples R China;

    Natl Inst Biol Sci Beijing 102206 Peoples R China;

    Beijing Normal Univ Coll Life Sci Beijing 100875 Peoples R China;

    Natl Inst Biol Sci Beijing 102206 Peoples R China;

    Natl Inst Biol Sci Beijing 102206 Peoples R China;

    Natl Inst Biol Sci Beijing 102206 Peoples R China;

    Beijing Normal Univ Coll Life Sci Beijing 100875 Peoples R China;

    Natl Inst Biol Sci Beijing 102206 Peoples R China;

    Natl Inst Biol Sci Beijing 102206 Peoples R China;

    Natl Inst Biol Sci Beijing 102206 Peoples R China;

    Natl Inst Biol Sci Beijing 102206 Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 内分泌腺疾病及代谢病;
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