Distinct Roles of HDAC3 in the Core Circadian Negative Feedback Loop Are Critical for Clock Function

Genetic depletion of Hdac3 results in low-amplitude circadian rhythms and dampened E-box-driven transcription.

• The BMAL1-CLOCK complex activates the transcription of Period and Cryptochrome genes.
• The PER-CRY complex interacts with BMAL1-CLOCK to repress its activity, closing the negative feedback loop.
• HDAC3 is essential for both the activation and repression processes of the circadian feedback loop without requiring its deacetylase activity.
• In the subjective morning, HDAC3 regulates BMAL1 stability to promote efficient transcriptional activation.
• In the subjective night, HDAC3 inhibits the degradation of CRY1 and enhances the association between BMAL1 and CRY1.

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