Figure 2.

The autoregulatory feedback loop of core clock genes. BMAL1:CLOCK binds E-box and enhances clock-controlled gene transcription, including mRNA transcripts for PER, CRY, REV-ERB, and ROR. In addition to extranuclear actions, PER:CRY suppresses BMAL1:CLOCK activity, inhibiting their own transcription. This ~24-h cycle is reinforced by other clock proteins; RORα increases transcription by binding RRE in the BMAL1 promoter, and REV-ERBα suppresses it. DEC proteins bind E-box and prevent their own transcription. Green = stimulatory action; red = inhibitory action; double lines = DNA; solid lines = mRNA transcripts.