REV-ERB

The nuclear receptors REV-ERBs consist of REV-ERBα and REV-ERBβ, which are encoded by Nr1d1 and Nr1d2 respectively. REV-ERBs lack the canonical nuclear receptor activation domain, the carboxy-terminal tail (helix 12) of the ligand-binding domain (LBD), and thus function as constitutive repressors of transcription and bind DNA response elements termed ‘ROREs ’. Like other nuclear receptors, REV-ERB activity can be regulated by ligands, including naturally occurring heme. The REV-ERBs link circadian rhythms and metabolism. REV-ERBα-deletion mice have defective circadian clocks and display a variety of metabolic abnormalities in many tissues.