Nuclear receptor Rev-erbα (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-erbα gene regulation is circadian, and Rev-erbα comprises a critical negative limb of the core circadian clock by directly repressing the expression of the positive clock component, Bmal1. Rev-erbα also regulates the metabolic gene pathway, thus serving as a heme sensor for coordination of circadian and metabolic pathways.
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