CLOCK, an essential pacemaker component, controls expression of the circadian transcription factor DBP

• Published in: Genes & development Vol. 14; no. 6; pp. 679 - 689
• Main Authors: Ripperger, J A, Shearman, L P, Reppert, S M, Schibler, U
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 15.03.2000
• Subjects: Animals; Base Sequence; circadian clocks; Circadian Rhythm; CLOCK protein; CLOCK Proteins; DBP protein; Deoxyribonuclease I - metabolism; DNA Primers; DNA-Binding Proteins; Gene Expression Regulation - physiology; Introns; Liver - metabolism; Mice; Mice, Mutant Strains; Molecular Sequence Data; Period1 gene; Research Paper; RNA, Messenger - genetics; RNA, Messenger - metabolism; Suprachiasmatic Nucleus - metabolism; Trans-Activators - physiology; Transcription Factors - genetics; Transcription, Genetic - physiology; Transfection
• ISSN: 0890-9369; 1549-5477
• DOI: 10.1101/gad.14.6.679

DBP, the founding member of the PAR leucine zipper transcription factor family, is expressed according to a robust daily rhythm in the suprachiasmatic nucleus and several peripheral tissues. Previous studies with mice deleted for the Dbp gene have established that DBP participates in the regulation of several clock outputs, including locomotor activity, sleep distribution, and liver gene expression. Here we present evidence that circadian Dbp transcription requires the basic helix-loop-helix-PAS protein CLOCK, an essential component of the negative-feedback circuitry generating circadian oscillations in mammals and fruit flies. Genetic and biochemical experiments suggest that CLOCK regulates Dbp expression by binding to E-box motifs within putative enhancer regions located in the first and second introns. Similar E-box motifs have been found previously in the promoter sequence of the murine clock gene mPeriod1. Hence, the same molecular mechanisms generating circadian oscillations in the expression of clock genes may directly control the rhythmic transcription of clock output regulators such as Dbp.