Redox Around the Clock

Abstract

Circadian rhythms are controlled by an evolutionarily conserved transcriptional feedback system whose activity fluctuates as a function of the 24-hour light-dark cycle. Extrinsic factors, such as changes in food intake, can advance or delay the circadian clock, but the mechanism by which this "entrainment" occurs remains unclear. A key regulator of circadian rhythms, Clock, is expressed in the suprachiasmatic nucleus (the brain region regarded as the master pacemaker) and regulates the expression of genes encoding other clock components. Reick et al. and Rutter et al. show that the NPAS2 transcription factor performs a function similar to Clock in the mammalian forebrain and that the DNA binding activity of both these transcription factors in vitro is regulated by the redox state of nicotinamide adenine dinucleotide (NAD) cofactors. Because changes in food intake are associated with changes in cellular redox state, the authors propose that redox control of Clock and NPAS2 activity may explain how food and other extrinsic factors entrain the molecular clock. A Perspective by Schibler et al. accompanies the two reports. M. Reick, J.A. Garcia, C. Dudley, S.L. McKnight, NPAS2: An analog of Clock operative in the mammalian forebrain. Science 293 , 506-509 (2001). [Abstract] [Full Text] J. Rutter, M. Reick, L.C. Wu, S.L. McKnight, Regulation of Clock and NPAS2 DNA binding by the redox state of NAD cofactors. Science 293 , 510-514 (2001). [Abstract] [Full Text] U. Schibler, J.A. Ripperger, S.A. Brown, Chronobiology--reducing time. Science 293: 437-438 (2001). [Full Text]