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

J. Rutter, M. Reick, L. C. Wu, S. L. McKnight

Research output: Contribution to journalArticle

698 Scopus citations

Abstract

Clock:BHAL1 and NPAS2:BHAL1 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 dock can be entrained by light, activity, or food. Here we show that the DNA-binding activity of the Clock:BHAL1 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 dock by direct modulation of cellular redox state.

Original languageEnglish (US)
Pages (from-to)510-514
Number of pages5
JournalScience
Volume293
Issue number5529
DOIs
StatePublished - Jul 20 2001

ASJC Scopus subject areas

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