Acetylation-mediated epigenetic regulation of glucocorticoid receptor activity: Circadian rhythm-associated alterations of glucocorticoid actions in target tissues

The circadian rhythm-related transcription factor Clock acetylates the glucocorticoid receptor, affecting its activity.

• Clock acetylates lysines in the hinge region of the glucocorticoid receptor, which contains a specific lysine cluster.
• This acetylation represses the transcriptional activity of the glucocorticoid receptor.
• The repression occurs in an inversely phased manner to the levels of circulating glucocorticoids throughout the day.
• Disruption of the CLOCK-regulated hypothalamic-pituitary-adrenal axis and peripheral glucocorticoid action may lead to functional hypercortisolism.
• Such disruptions could be linked to conditions like chronic stress, frequent time zone changes, or night-shift work.
• The acetylation process may play a crucial role in ensuring proper glucocorticoid action, impacting human health and longevity.

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