Fig. 3.

Model Illustrating the Proposed Mechanism for Heme Modulation of REV-ERB Activity

REV-ERB functions as a receptor for heme. REV-ERB recognizes and binds specific DNA sequences known as RevREs in the promoter regions of its target genes. Heme binds directly to the LBD of REV-ERB and increases the affinity of the receptor for the corepressor NCoR. When NCoR is recruited to the promoter by REV-ERB, the gene is repressed due to the histone deacetylase activity that is associated with the NCoR/histone deacetylase complex. Modulation of REV-ERB target genes is associated with regulation of physiological functions such as lipid metabolism, circadian rhythm and cellular differentiation. DBD, DNA-binding domain.