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. 2001 Jul 20;293(5529):510-4.
doi: 10.1126/science.1060698. Epub 2001 Jul 5.

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

J Rutter  1 , M Reick, L C Wu, S L McKnight
Affiliations

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

J Rutter et al. Science. .

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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