Abstract:
:Circadian rhythms in mammals are generated by a transcriptional negative feedback loop that is driven primarily by oscillations of PER and CRY, which inhibit their own transcriptional activators, CLOCK and BMAL1. Current models posit that CRY is the dominant repressor, while PER may play an accessory role. In this study, however, constitutive expression of PER, and not CRY1, severely disrupted the clock in fibroblasts and liver. Furthermore, constitutive expression of PER2 in the brain and SCN of transgenic mice caused a complete loss of behavioral circadian rhythms in a conditional and reversible manner. These results demonstrate that rhythmic levels of PER2, rather than CRY1, are critical for circadian oscillations in cells and in the intact organism. Our biochemical evidence supports an elegant mechanism for the disparity: PER2 directly and rhythmically binds to CLOCK:BMAL1, while CRY only interacts indirectly; PER2 bridges CRY and CLOCK:BMAL1 to drive the circadian negative feedback loop.
journal_name
Mol Celljournal_title
Molecular cellauthors
Chen R,Schirmer A,Lee Y,Lee H,Kumar V,Yoo SH,Takahashi JS,Lee Cdoi
10.1016/j.molcel.2009.10.012subject
Has Abstractpub_date
2009-11-13 00:00:00pages
417-30issue
3eissn
1097-2765issn
1097-4164pii
S1097-2765(09)00777-1journal_volume
36pub_type
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