How core body clock proteins influence glucocorticoid receptor activity

CLOCK/BMAL1 reduces maximal GR transactivation and efficacy in target tissues.

• CLOCK/BMAL1, core components of the circadian clock, interact with DNA to modulate GC action.
• PER1 and CRY1, targets of CLOCK/BMAL1, decrease maximal GR transactivation without affecting efficacy.
• BMAL1 or PERs-deficient mouse embryonic fibroblasts show increased GRE-dependent transcription activity.
• Expression of endogenous GC target genes is negatively correlated with CLOCK/BMAL1 activity.
• Findings suggest that circadian regulation of GC sensitivity may be relevant to human health and disease.

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