Rev-Erb receptors are orphan nuclear receptors belonging to the NR1D receptor family. There are two family members, Rev-Erbα (NR1D1) and Rev-Erbβ (NR1D2). Rev-Erb receptors are thought to share many target genes with retinoic acid receptor-related orphan receptors (RORs), and both groups recognize a number of the same DNA response elements. Furthermore, Rev-Erbs and RORs are coexpressed in adipose tissue, liver, skeletal muscle and brain, and play a central role in circadian rhythm and lipid metabolism.
Rev-Erb receptors act as repressors of Bmal1 transcription, in opposition to RORs. Bmal1 is integral to the maintenance of circadian rhythms: the Bmal1/Clock heterodimer activates expression of period (Per) and cryptochrome (Cry) genes. When expression reaches critical levels a negative feedback loop is generated that inhibits Bmal1/Clock heterodimers. Consequently, both Rev-Erb receptors and RORs are principal regulators of the feedback loops that underlie circadian rhythms.
Rev-Erb receptors are unlike other nuclear hormone receptors in that they lack an AF2 region in their ligand-binding domain, a feature that is necessary for transcriptional activation. Instead, they function as transcriptional corepressors, and can recruit the NCoR/HDAC3 corepressor complex. Heme has been shown to bind Rev-Erb receptors, and to modulate their repressive activity by increasing the recruitment of NCoR/HDAC3 to DNA response elements in promoter regions of Rev-Erb target genes. In addition, heme promotes proteasomal degradation of the receptor, a critical event in adipogenesis. The expression of Rev-Erbα in adipose tissue is key in the regulation of adipogenesis and can be modulated by PPARγ activation.
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|Gene||Species||Gene Symbol||Gene Accession No.||Protein Accession No.|
|Nuclear receptor subfamily 1, group D, member 1||Human||NR1D1||NM_021724||P20393|
|Nuclear receptor subfamily 1, group D, member 2||Human||NR1D2||NM_005126||Q14995|
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