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Rhythmic PER abundance defines a critical nodal point for negative feedback within the circadian clock mechanism.

Title: Rhythmic PER abundance defines a critical nodal point for negative feedback within the circadian clock mechanism.
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Name(s): Chen, Rongmin, author
Schirmer, Aaron, author
Lee, Yongjin, author
Lee, Hyeongmin, author
Kumar, Vivek, author
Yoo, Seung-Hee, author
Takahashi, Joseph S, author
Lee, Choogon, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2009-11-13
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: 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.
Identifier: FSU_pmch_19917250 (IID), 10.1016/j.molcel.2009.10.012 (DOI), PMC3625733 (PMCID), 19917250 (RID), 19917250 (EID), S1097-2765(09)00777-1 (PII)
Grant Number: R01 NS053616-04, R01 NS053616-03, R01 NS053616, R01 NS053616-01A1, , P50 MH074924-05, R01 NS053616-02, P50 MH074924, NS-053616
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3625733.
Subject(s): ARNTL Transcription Factors/genetics
ARNTL Transcription Factors/metabolism
Animals
Biological Clocks/genetics
Biological Clocks/physiology
CLOCK Proteins/genetics
CLOCK Proteins/metabolism
Cells, Cultured
Circadian Rhythm/genetics
Circadian Rhythm/physiology
Cryptochromes/genetics
Cryptochromes/metabolism
Fibroblasts/cytology
Fibroblasts/metabolism
Gene Expression Profiling
Green Fluorescent Proteins/genetics
Green Fluorescent Proteins/metabolism
Immunoblotting
Liver/metabolism
Luciferases/genetics
Luciferases/metabolism
Luminescent Measurements
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Period Circadian Proteins/genetics
Period Circadian Proteins/metabolism
Protein Binding
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_19917250
Owner Institution: FSU
Is Part Of: Molecular cell.
1097-4164
Issue: iss. 3, vol. 36

Choose the citation style.
Chen, R., Schirmer, A., Lee, Y., Lee, H., Kumar, V., Yoo, S. -H., … Lee, C. (2009). Rhythmic PER abundance defines a critical nodal point for negative feedback within the circadian clock mechanism. Molecular Cell. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_19917250