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Updated: May 7, 2026
11:56
In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells
Published on: September 28, 2017
A positive feedback loop links circadian clock factor CLOCK-BMAL1 to the basic transcriptional machinery
Laura Lande-Diner1, Cyril Boyault, Jin Young Kim
1Department of Neurobiology, Harvard Medical School, Boston, MA 02115.
Summary
The circadian clock relies on a negative feedback loop. Researchers discovered TRAP150 acts as a crucial coactivator, promoting CLOCK-BMAL1 activity and establishing a positive feedback loop essential for rhythm timing.
Area of Science:
- Chronobiology
- Molecular Biology
- Genetics
Background:
- Mammalian circadian clocks operate via a negative feedback loop.
- The CLOCK-BMAL1 transcription factor drives expression of its inhibitors, PERIOD and CRYPTOCHROME proteins.
- The mechanism timing CLOCK-BMAL1 reactivation after inhibitor turnover is unknown.
Purpose of the Study:
- To elucidate the mechanism behind CLOCK-BMAL1 reactivation in mammalian circadian rhythms.
- To identify novel components involved in the positive regulation of circadian transcription.
Main Methods:
- Investigated the interaction of BMAL1 with other proteins using mouse models.
- Assessed the role of TRAP150 in CLOCK-BMAL1 transcriptional activity.
- Examined the impact of TRAP150 depletion on circadian rhythm parameters.
Main Results:
- Identified TRAP150 (THRAP3) as a component of mouse BMAL1 complexes.
- TRAP150 functions as a selective coactivator for CLOCK-BMAL1, enhancing gene binding and transcriptional machinery interaction.
- Depletion of TRAP150 resulted in attenuated circadian rhythms with longer periods.
Conclusions:
- TRAP150 is a critical positive clock element, essential for robust circadian rhythmicity.
- TRAP150 establishes a positive feedback loop, providing a mechanism for timing circadian transcription reactivation.
- This discovery offers new insights into the molecular regulation of mammalian circadian clocks.
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