Relationship between circadian oscillations of Rev-erbα expression and intracellular levels of its ligand, heme

The nuclear hormone receptors, REV-ERBα [NR1D1] and REV-ERBβ [NR1D1], were recently demonstrated to be receptors for the porphyrin, heme. Heme regulates the ability of these receptors to repress transcription of their target genes via modulation of the affinity of the receptor’s ligand binding domain for the corepressor, NCoR. The REV-ERBs function as critical components of the mammalian clock and their expression oscillates in a circadian manner. Here, we show that in NIH3T3 cells intracellular heme levels also oscillate in a circadian fashion. These data are the first to show the temporal relationship of intracellular heme levels to the expression of its receptor, Rev-erbα, and suggest that the rapid oscillations in heme levels may an important component regulating REV-ERB transcriptional activity.