Publication Date:
2001-07-07
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rutter, J -- Reick, M -- Wu, L C -- McKnight, S L -- 1RO1MH59388/MH/NIMH NIH HHS/ -- NIH5-T32-GM08-291-12/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Jul 20;293(5529):510-4. Epub 2001 Jul 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Texas-Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9152, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11441146" target="_blank"〉PubMed〈/a〉
Keywords:
ARNTL Transcription Factors
;
Animals
;
Aryl Hydrocarbon Receptor Nuclear Translocator
;
Basic Helix-Loop-Helix Transcription Factors
;
Biological Clocks
;
CLOCK Proteins
;
Cell Line
;
Circadian Rhythm
;
DNA/*metabolism
;
*DNA-Binding Proteins
;
Dimerization
;
Helix-Loop-Helix Motifs
;
Humans
;
L-Lactate Dehydrogenase/genetics/metabolism
;
Mice
;
NAD/*metabolism/pharmacology
;
NADP/*metabolism/pharmacology
;
Nerve Tissue Proteins/chemistry/*metabolism
;
Oxidation-Reduction
;
*Receptors, Aryl Hydrocarbon
;
Recombinant Proteins/metabolism
;
Trans-Activators/chemistry/*metabolism
;
Transcription Factors/chemistry/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
