期刊
SCIENCE
卷 288, 期 5468, 页码 1013-1019出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.288.5468.1013
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资金
- NHLBI NIH HHS [HL07901] Funding Source: Medline
- NICHD NIH HHS [R37 HD14427] Funding Source: Medline
- NINDS NIH HHS [R01 NS39303] Funding Source: Medline
We show that, in the mouse, the core mechanism for the master circadian clock consists of interacting positive and negative transcription and translation feedback Loops. Analysis of Clock/Clock mutant mice, homozygous period2(Brdm1) mutants, and Cryptochrome-deficient mice reveals substantially altered Small rhythms, consistent with a dominant role of PERIOD2 in the positive regulation of the Bmal1 Loop. In vitro analysis of CRYPTOCHROME inhibition of CLOCK: BMAL1-mediated transcription shows that the inhibition is through direct protein:protein interactions, independent of the PERIOD and TIMELESS proteins. PERIOD2 is a positive regulator of the Bmal1 Loop, and CRYPTOCHROMES are the negative regulators of the Period and Cryptochrome cycles.
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