Cited by 1,059Circadian rhythm and melatoninPlant Molecular Biology ResearchSleep and Wakefulness Research

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

Rutter, Jared, Reick, Martin, Wu, Leeju C., McKnight, Steven L.·2001·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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Crossref · 10.1126/science.1060698

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  • In vivo NAD levels are subjected to daily variations, thereby giving rhythmic input to the genetic clock.

    “Interestingly, in vivo NAD levels are subjected to daily variations, thereby giving rhythmic input to the genetic clock [44–46]”

    From Circadian control of glucose metabolism (2014) · cites this paper as [45]

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Authors
Rutter, J., Reick, M., Wu, L. C., & McKnight, S. L.
Affiliations
The University of Texas Southwestern Medical Center (US)
Corresponding author
  • Rutter, Jared
  • Reick, Martin
  • McKnight, Steven L.
Venue
Science
Published
2001-07-20
Volume
293
Issue
5529
Pages
510-514
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2063041018
Cited by
1,059
References
39
Citations by year
2026: 26 · 2025: 26 · 2024: 28 · 2023: 32 · 2022: 32 · 2021: 32 · 2020: 40 · 2019: 26 · 2018: 38 · 2017: 42 · 2016: 39 · 2015: 42 · 2014: 44 · 2013: 68 · 2012: 42
FWCI
18.50
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute of Mental Health (R01MH059388, 1RO1MH59388)
  • National Institute of General Medical Sciences (NIH5-T32-GM08-291-12)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
Keywords
circadian clock, NPAS2, Bmal1, clocks, NAD+ cofactor, redox state, DNA binding, transcription factor heterodimer, NADPH, NADH, clock entrainment, food entrainment, neuronal activity
MeSH terms
Animals, Biological Clocks, Cell Line, Circadian Rhythm, DNA, DNA-Binding Proteins, Humans, L-Lactate Dehydrogenase, NAD, NADP, Nerve Tissue Proteins, Oxidation-Reduction, Recombinant Proteins, Transcription Factors, Trans-Activators, Helix-Loop-Helix Motifs, Receptors, Aryl Hydrocarbon, Dimerization, Mice, Aryl Hydrocarbon Receptor Nuclear Translocator, Basic Helix-Loop-Helix Proteins, CLOCK Proteins, ARNTL Transcription Factors

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