Nuclear receptor Rev-erbalpha: a heme receptor that coordinates circadian rhythm and metabolism

Nuclear receptor Rev-erbalpha (NR1D1), previously considered to be an orphan nuclear receptor, is a receptor for heme, which promotes transcriptional repression via recruitment of the NCoR-HDAC3 corepressor complex. Rev-erbalpha gene regulation is circadian, and Rev-erbalpha comprises a critical negative limb of the core circadian clock by directly repressing the expression of the positive clock component, Bmal1. Rev-erbalpha also regulates the metabolic gene pathway, thus serving as a heme sensor for coordination of circadian and metabolic pathways.