Figure 1. Rev-erbα coordinates circadian rhythm and metabolic pathways in a heme-dependent mode.

The binding elements of Rev-erbα, called ROREs, are present in core clock genes and also in important metabolic genes. Heme, a physiological ligand of Rev-erbα, promotes recruitment of the NCoR-HDAC3 corepressor complex to Rev-erbα homodimers bound to target genes and enhances Rev-erbα-mediated repression of those target genes. Heme binding to Rev-erbα induces the feedback inhibition of its own biosynthesis.