Compensation for intracellular environment in expression levels of mammalian circadian clock genes

Sci Rep. 2014 Feb 7:4:4032. doi: 10.1038/srep04032.


The circadian clock is driven by transcriptional oscillation of clock genes in almost all body cells. To investigate the effect of cell type-specific intracellular environment on the circadian machinery, we examined gene expression profiles in five peripheral tissues. As expected, the phase relationship between expression rhythms of nine clock genes was similar in all tissues examined. We also compared relative expression levels of clock genes among tissues, and unexpectedly found that quantitative variation remained within an approximately three-fold range, which was substantially smaller than that of metabolic housekeeping genes. Interestingly, circadian gene expression was little affected even when fibroblasts were cultured with different concentrations of serum. Together, these findings support a hypothesis that expression levels of clock genes are quantitatively compensated for the intracellular environment, such as redox potential and metabolite composition. However, more comprehensive studies are required to reach definitive conclusions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors / biosynthesis
  • Actins / biosynthesis
  • Animals
  • COS Cells
  • Cell Line
  • Chlorocebus aethiops
  • Circadian Clocks / genetics*
  • Circadian Rhythm / genetics*
  • Cryptochromes / biosynthesis
  • Gene Expression
  • Gene Expression Profiling
  • Gene Expression Regulation / genetics*
  • HEK293 Cells
  • Hep G2 Cells
  • Humans
  • Mice
  • NIH 3T3 Cells
  • Period Circadian Proteins / biosynthesis
  • Period Circadian Proteins / genetics
  • RNA, Ribosomal, 18S / biosynthesis


  • ARNTL Transcription Factors
  • BMAL1 protein, human
  • Actins
  • CRY1 protein, human
  • Cryptochromes
  • PER2 protein, human
  • PER3 protein, human
  • Period Circadian Proteins
  • RNA, Ribosomal, 18S