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Updated: Aug 11, 2026
Monitoring Cell-autonomous Circadian Clock Rhythms of Gene Expression Using Luciferase Bioluminescence Reporters
Published on: September 27, 2012
Direct association between mouse PERIOD and CKIepsilon is critical for a functioning circadian clock
Choogon Lee1, David R Weaver, Steven M Reppert
1Department of Neurobiology, LRB-728, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
Abstract:
The mPER1 and mPER2 proteins have important roles in the circadian clock mechanism, whereas mPER3 is expendable. Here we examine the posttranslational regulation of mPER3 in vivo in mouse liver and compare it to the other mPER proteins to define the salient features required for clock function. Like mPER1 and mPER2, mPER3 is phosphorylated, changes cellular location, and interacts with other clock proteins in a time-dependent manner. Consistent with behavioral data from mPer2/3 and mPer1/3 double-mutant mice, either mPER1 or mPER2 alone can sustain rhythmic posttranslational events. However, mPER3 is unable to sustain molecular rhythmicity in mPer1/2 double-mutant mice. Indeed, mPER3 is always cytoplasmic and is not phosphorylated in the livers of mPer1-deficient mice, suggesting that mPER3 is regulated by mPER1 at a posttranslational level. In vitro studies with chimeric proteins suggest that the inability of mPER3 to support circadian clock function results in part from lack of direct and stable interaction with casein kinase Iepsilon (CKIepsilon). We thus propose that the CKIepsilon-binding domain is critical not only for mPER phosphorylation but also for a functioning circadian clock.
Insights
Mouse PER3 protein is regulated by mPER1 at a posttranslational level, impacting circadian clock function. This regulation is crucial for maintaining molecular rhythmicity and proper clock function.
Area of Science:
- Chronobiology
- Molecular Biology
- Biochemistry
Background:
- The circadian clock mechanism relies on core clock proteins like mPER1, mPER2, and mPER3.
- While mPER1 and mPER2 are essential, mPER3 has been considered expendable in circadian rhythms.
Purpose of the Study:
- To investigate the posttranslational regulation of mPER3 in mouse liver.
- To compare mPER3 regulation with mPER1 and mPER2 to identify key features for circadian clock function.
Main Methods:
- In vivo studies in mouse liver.
- Analysis of protein phosphorylation and cellular localization.
- Interaction studies with other clock proteins.
- In vitro studies using chimeric proteins.
Main Results:
- mPER3 exhibits time-dependent phosphorylation, cellular translocation, and interactions, similar to mPER1 and mPER2.
- mPER1 or mPER2 alone can maintain rhythmic posttranslational events.
- mPER3 cannot sustain molecular rhythmicity in mPer1/2 double-mutant mice.
- mPER3 is constitutively cytoplasmic and unphosphorylated in mPer1-deficient mice.
- mPER3's inability to support clock function is partly due to a lack of direct interaction with casein kinase Iepsilon (CKIepsilon).
Conclusions:
- mPER3 is regulated by mPER1 at a posttranslational level.
- The casein kinase Iepsilon (CKIepsilon)-binding domain is critical for mPER phosphorylation and circadian clock function.
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