Figure 8.

Rev-erbα and Rev-erbβ cooperate in regulating core clock function and mediating the interplay between circadian rhythm and metabolism. The Rev-erbs are central repressors of both the positive (Bmal1) and the negative (Cry1 and Rev-erbα) limb of the core clock. In addition, the Rev-erbs mediate the interplay between the cellular clock and metabolism together with BMAL1 and CLOCK/NPAS2. Note that other core clock components (shown as PER, CRY, and BMAL in the model for simplicity) all have homologs (PER1–3, CRY1/2, and BMAL1/2) that, like the two Rev-erb subtypes, function as a backup system.