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    Science. 2001 Jul 20;293(5529):510-4. Epub 2001 Jul 5.

    Regulation of clock and NPAS2 DNA binding by the redox state of NAD cofactors.

    Rutter J, Reick M, Wu LC, McKnight SL.

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    Department of Biochemistry, University of Texas-Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9152, USA.

    Abstract

    Clock:BMAL1 and NPAS2:BMAL1 are heterodimeric transcription factors that control gene expression as a function of the light-dark cycle. Although built to fluctuate at or near a 24-hour cycle, the clock can be entrained by light, activity, or food. Here we show that the DNA-binding activity of the Clock:BMAL1 and NPAS2:BMAL1 heterodimers is regulated by the redox state of nicotinamide adenine dinucleotide (NAD) cofactors in a purified system. The reduced forms of the redox cofactors, NAD(H) and NADP(H), strongly enhance DNA binding of the Clock:BMAL1 and NPAS2:BMAL1 heterodimers, whereas the oxidized forms inhibit. These observations raise the possibility that food, neuronal activity, or both may entrain the circadian clock by direct modulation of cellular redox state.

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    PMID:
    11441146
    [PubMed - indexed for MEDLINE]

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