Fig. 3

a The basic mammalian circadian clock loop consists of transcription factors BMAL1 and CLOCK which express PER (PER1, PER2, PER3), CRY (CRY1, CRY2), REV-ERB (NR1D1, NR1D2) and ROR (RORA, RORB, RORC) genes. The PER and CRY proteins accumulate and repress BMAL1/CLOCK activity before being degraded through a mechanism involving casein kinases and the proteasome, which allows BMAL1 and CLOCK activity to resume. In a second loop, the expressed ROR and REV-ERB proteins act to enhance or repress expression of BMAL1 gene. Genes/mRNAs indicated in italics, proteins indicated by colored ovals. b Circadian genes demonstrate cyclical expression over a 24 h period. BMAL1, brain and muscle aryl hydrocarbon receptor nuclear translocator (ARNT)-like 1; CLOCK, circadian locomotor output cycles kaput; PER, period; ROR, RAR-related orphan receptor