Identification of transcriptional regulatory elements required for the Mup2 expression in circadian clock mutant mice

Biochem Biophys Res Commun. 2011 Jul 15;410(4):834-40. doi: 10.1016/j.bbrc.2011.06.074. Epub 2011 Jun 15.


The suprachiasmatic nuclei in the mammalian brain function as the regulators of circadian rhythm and coordinate the peripheral oscillators. Losses of clock genes alter gene expression and behavior. Here, we investigated whether disruption of the circadian clock and glucocorticoid signals would influence the gene expression of major urinary protein (Mup) in mice. Both Mup2 mRNA and protein showed biphasic rhythms with similar phase relationships. However, the peak of the rhythm is shifted in mPeriod2 circadian clock mutant mice. We identified two E-boxes and one glucocorticoid response element (GRE) as regulatory elements for Mup2 transcription. While CLOCK binds to the E-boxes constantly, glucocorticoid receptor was capable of binding to the GRE in a timely manner. All together, our results indicate that Mup2 expression is regulated by both the circadian clock and glucocorticoid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors / metabolism
  • Animals
  • CLOCK Proteins / metabolism
  • Chromatin Immunoprecipitation
  • Circadian Clocks / genetics
  • Circadian Clocks / physiology*
  • Gene Expression Regulation*
  • Glucocorticoids / pharmacology
  • Glucocorticoids / physiology*
  • Liver / metabolism
  • Mice
  • Mice, Knockout
  • NIH 3T3 Cells
  • Period Circadian Proteins / genetics
  • Protein Multimerization
  • Proteins / genetics*
  • Regulatory Elements, Transcriptional*
  • Transcription, Genetic


  • ARNTL Transcription Factors
  • Arntl protein, mouse
  • Glucocorticoids
  • Per2 protein, mouse
  • Period Circadian Proteins
  • Proteins
  • major urinary proteins
  • CLOCK Proteins
  • Clock protein, mouse