論文

査読有り
2003年10月

Genome-wide expression analysis of mouse liver reveals CLOCK-regulated circadian output genes

JOURNAL OF BIOLOGICAL CHEMISTRY
  • K Oishi
  • ,
  • K Miyazaki
  • ,
  • K Kadota
  • ,
  • R Kikuno
  • ,
  • T Nagase
  • ,
  • G Atsumi
  • ,
  • N Ohkura
  • ,
  • T Azama
  • ,
  • M Mesaki
  • ,
  • S Yukimasa
  • ,
  • H Kobayashi
  • ,
  • C Iitaka
  • ,
  • T Umehara
  • ,
  • M Horikoshi
  • ,
  • T Kudo
  • ,
  • Y Shimizu
  • ,
  • M Yano
  • ,
  • M Monden
  • ,
  • K Machida
  • ,
  • J Matsuda
  • ,
  • S Horie
  • ,
  • T Todo
  • ,
  • N Ishida

278
42
開始ページ
41519
終了ページ
41527
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1074/jbc.M304564200
出版者・発行元
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

CLOCK is a positive component of a transcription/ translation-based negative feedback loop of the central circadian oscillator in the suprachiasmatic nucleus in mammals. To examine CLOCK-regulated circadian transcription in peripheral tissues, we performed microarray analyses using liver RNA isolated from Clock mutant mice. We also compared expression profiles with those of Cryptochromes (Cry1 and Cry2) double knockout mice. We identified more than 100 genes that fluctuated from day to night and of which expression levels were decreased in Clock mutant mice. In Cry-deficient mice, the expression levels of most CLOCK-regulated genes were elevated to the upper range of normal oscillation. Most of the screened genes had a CLOCK/BMAL1 binding site (E box) in the 5'-flanking region. We found that CLOCK was absolutely concerned with the circadian transcription of one type of liver genes ( such as DBP, TEF, and Usp2) and partially with another ( such as mPer1, mPer2, mDec1, Nocturnin, P450 oxidoreductase, and FKBP51) because the latter were damped but remained rhythmic in the mutant mice. Our results showed that CLOCK and CRY proteins are involved in the transcriptional regulation of many circadian output genes in the mouse liver. In addition to being a core component of the negative feedback loop that drives the circadian oscillator, CLOCK also appears to be involved in various physiological functions such as cell cycle, lipid metabolism, immune functions, and proteolysis in peripheral tissues.


リンク情報
DOI
https://doi.org/10.1074/jbc.M304564200
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000185847200132&DestApp=WOS_CPL
ID情報
  • DOI : 10.1074/jbc.M304564200
  • ISSN : 0021-9258
  • Web of Science ID : WOS:000185847200132

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