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Rhythmic PER Abundance Defines a Critical Nodal Point for Negative Feedback within the Circadian Clock Mechanism
Rhythmic levels of PER protein play a key role in the circadian clock's feedback control
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Abstract
Constitutive expression of PER2 in the brain and SCN of transgenic mice caused a complete loss of behavioral circadian rhythms.
- Circadian rhythms in mammals are influenced by a transcriptional negative feedback loop involving PER and CRY proteins.
- Current models suggest that CRY is the main repressor of this feedback loop, while PER has a secondary role.
- However, disrupting the clock in fibroblasts and liver was primarily linked to the expression of PER, not CRY1.
- Rhythmic levels of PER2 are shown to be essential for maintaining circadian oscillations in both cells and living organisms.
- Biochemical evidence indicates that PER2 directly and rhythmically binds to the CLOCK:BMAL1 complex, while CRY interacts indirectly.
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