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Updated: May 8, 2026

Monitoring Cell-autonomous Circadian Clock Rhythms of Gene Expression Using Luciferase Bioluminescence Reporters
Published on: September 27, 2012
Circadian regulator CLOCK is a histone acetyltransferase
Masao Doi1, Jun Hirayama, Paolo Sassone-Corsi
1Institut de Génétique et de Biologie Moléculaire et Cellulaire, B.P. 10142, 67404 Illkirch, Strasbourg, France.
The CLOCK protein, a key part of the circadian clock, possesses histone acetyltransferase (HAT) activity. This HAT function is vital for regulating circadian rhythm and clock gene expression, revealing a link between chromatin remodeling and cellular physiology.
Area of Science:
- Chronobiology
- Molecular Biology
- Epigenetics
Background:
- Circadian rhythmicity is controlled by molecular machinery generating time-specific gene transcription.
- The function of chromatin remodeling in the circadian clock remains largely unknown.
Purpose of the Study:
- To investigate the role of the CLOCK protein in circadian rhythm regulation.
- To determine if CLOCK possesses enzymatic activity related to chromatin modification.
Main Methods:
- Assessed the histone acetyltransferase (HAT) activity of the CLOCK protein.
- Examined the effect of CLOCK's HAT activity on circadian rhythmicity in Clock mutant cells.
- Analyzed the interaction between CLOCK and its partner BMAL1.
Main Results:
- Identified CLOCK as a novel DNA-binding protein with intrinsic histone acetyltransferase (HAT) activity.
- Demonstrated that BMAL1 enhances the HAT activity of CLOCK.
- Showed that CLOCK's HAT activity is essential for restoring circadian rhythm and activating clock genes in mutant cells.
Conclusions:
- CLOCK functions as a DNA-binding HAT, implicating chromatin remodeling in the core circadian clock mechanism.
- Histone acetylation is directly linked to cellular physiology and circadian rhythm.
- Unveiled novel connections between epigenetic regulation and biological timing.
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