Circadian rhythm transcription factor CLOCK regulates the transcriptional activity of the glucocorticoid receptor by acetylating its hinge region lysine cluster: potential physiological implications

Jan 15, 2009FASEB journal : official publication of the Federation of American Societies for Experimental Biology

The body clock protein CLOCK controls stress hormone receptor activity by modifying a key region, with possible health effects

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Abstract

CLOCK/BMAL1 may act as a reverse-phase negative regulator of glucocorticoid action.

  • Glucocorticoids, regulated by the hypothalamic-pituitary-adrenal axis, influence the function of nearly all organs and tissues.
  • CLOCK and BMAL1 are transcription factors that generate circadian rhythms and may regulate glucocorticoid receptor (GR) activity.
  • Transcriptional activity of GR fluctuated in a circadian manner, inversely correlating with CLOCK/BMAL1 mRNA expression.
  • CLOCK physically interacts with GR, suppressing its ability to bind to DNA by modifying specific lysine residues.
  • These findings suggest that circadian rhythms in peripheral tissues could modulate the diverse actions of glucocorticoids throughout the body.

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