Role of the CLOCK protein in the mammalian circadian mechanism

Nicholas Gekakis, David Staknis, Hubert B. Nguyen, Fred C. Davis, Lisa D Wilsbacher, David P. King, Joseph S. Takahashi, Charles J. Weitz*

*Corresponding author for this work

Research output: Contribution to journalArticle

1347 Scopus citations

Abstract

The mouse Clock gene encodes a bHLH-PAS protein that regulates circadian rhythms and is related to transcription factors that act as heterodimers. Potential partners of CLOCK were isolated in a two-hybrid screen, and one, BMAL1, was coexpressed with CLOCK and PER1 at known circadian clock sites in brain and retina. CLOCK-BMAL1 heterodimers activated transcription from E- box elements, a type of transcription factor-binding site, found adjacent to the mouse per1 gene and from an identical E-box known to be important for per gene expression in Drosophila. Mutant CLOCK from the dominant-negative Clock allele and BMAL1 formed heterodimers that bound DNA but failed to activate transcription. Thus, CLOCK-BMAL1 heterodimers appear to drive the positive component of per transcriptional oscillations, which are thought to underlie circadian rhythmicity.

Original languageEnglish (US)
Pages (from-to)1564-1569
Number of pages6
JournalScience
Volume280
Issue number5369
DOIs
StatePublished - Jun 5 1998

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    Gekakis, N., Staknis, D., Nguyen, H. B., Davis, F. C., Wilsbacher, L. D., King, D. P., Takahashi, J. S., & Weitz, C. J. (1998). Role of the CLOCK protein in the mammalian circadian mechanism. Science, 280(5369), 1564-1569. https://doi.org/10.1126/science.280.5369.1564