title: Reciprocal Regulation between the Circadian Clock and Hypoxia Signaling at the Genome Level in Mammals.
abstract: 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.
authors: College of Life Sciences, Beijing Normal University, Beijing 100875, China; National Institute of Biological Sciences, Beijing 102206, China.
authors: Yaling
authors: Y
authors: Wu
authors: National Institute of Biological Sciences, Beijing 102206, China; PTN graduate program, School of Life Sciences, Peking University, Beijing 100871, China.
authors: Dingbin
authors: D
authors: Tang
authors: College of Life Sciences, Beijing Normal University, Beijing 100875, China; National Institute of Biological Sciences, Beijing 102206, China.
authors: Na
authors: N
authors: Liu
authors: National Institute of Biological Sciences, Beijing 102206, China.
authors: Wei
authors: W
authors: Xiong
authors: National Institute of Biological Sciences, Beijing 102206, China.
authors: Huanwei
authors: H
authors: Huang
authors: National Institute of Biological Sciences, Beijing 102206, China.
authors: Yang
authors: Y
authors: Li
authors: College of Life Sciences, Beijing Normal University, Beijing 100875, China; National Institute of Biological Sciences, Beijing 102206, China.
authors: Zhixiong
authors: Z
authors: Ma
authors: National Institute of Biological Sciences, Beijing 102206, China.
authors: Haijiao
authors: H
authors: Zhao
authors: National Institute of Biological Sciences, Beijing 102206, China.
authors: Peihao
authors: P
authors: Chen
authors: National Institute of Biological Sciences, Beijing 102206, China.
authors: Xiangbing
authors: X
authors: Qi
authors: National Institute of Biological Sciences, Beijing 102206, China. Electronic address: zhangerquan@nibs.ac.cn.
authors: Eric Erquan
authors: EE
authors: Zhang
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D047369:Chromatin Immunoprecipitation; D057906:Circadian Clocks / Q000235:genetics*; D004195:Disease Models, Animal; D024721:E-Box Elements / Q000235:genetics; D005786:Gene Expression Regulation; D016678:Genome; D057809:HEK293 Cells; D006801:Humans; D000860:Hypoxia / Q000235:genetics*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D008322:Mammals / Q000235:genetics*; D051379:Mice; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D056930:ARNTL Transcription Factors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins