Figure 1

Regulatory elements of mammalian circadian gene expression. A systems-level approach has identified the transcriptional circuit controlling circadian gene expression. The E/E3 box, the DBP/E4BP4-binding element (D box), and the RevErbA/ROR-regulatory element (RRE) are upstream regulatory elements in the genes indicated, and function alone or in combination throughout the 24-hour cycle to generate five phases of gene expression. The genes shown encode the following proteins: Arntl, aryl hydrocarbon receptor nuclear translocator-like protein; Bhlhb2 and Bhlhb3, basic helix-loop-helix domain containing proteins, class B; Clock, circadian locomotor output cycles kaput protein; Cry1, cryptochrome 1; Dpb, D-site albumin promoter-binding protein; Nr1d1 and Nr1d2, nuclear receptor subfamily 1 group D proteins; Npas2, neuronal PAS domain protein 2; Nfil3, nuclear factor, interleukin-3-regulated; Per1-Per3, period homologs; Rora, Rorb and Rorc, retinoic acid receptor-related orphan receptors alpha, beta, and gamma.