Abstract
Heterodimers of CLOCK and BMAL1, bHLH-PAS transcription factors, are believed to be the major transcriptional regulators of the circadian clock mechanism in mammals. However, a recent study shows that CLOCK-deficient mice continue to exhibit robust behavioral and molecular rhythms. Here we report that the transcription factor NPAS2 (MOP4) is able to functionally substitute for CLOCK in the master brain clock in mice to regulate circadian rhythmicity.
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Acknowledgements
We thank C.M. Lambert for technical assistance, and S.L. McKnight and J.S. Takahashi for providing the mice we used to establish colonies of Npas2 mutant mice and mPer2::Luciferase reporter mice, respectively. This work was supported by US National Institutes of Health (NIH) grants R01 NS047141 (S.M.R.) and R01 NS056125 (D.R.W.). J.P.D. was supported in part by NIH National Research Service Award F32 GM074277.
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Supplementary information
Supplementary Fig. 1
Raw luciferase activity data from the SCN prior to normalization and 24-h trend subtraction. (PDF 104 kb)
Supplementary Fig. 2
Quantitative real time PCR (qPCR) detection of Npas2 expression in the SCN. (PDF 56 kb)
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DeBruyne, J., Weaver, D. & Reppert, S. CLOCK and NPAS2 have overlapping roles in the suprachiasmatic circadian clock. Nat Neurosci 10, 543–545 (2007). https://doi.org/10.1038/nn1884
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DOI: https://doi.org/10.1038/nn1884
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