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. Author manuscript; available in PMC: 2016 May 12.
Published in final edited form as: Nat Rev Drug Discov. 2014 Mar;13(3):197–216. doi: 10.1038/nrd4100

Figure 2. Molecular mechanism of action of the RORs and REV-ERBs.

Figure 2

Retinoic acid receptor-related orphan receptors (RORs) and REV-ERBs are involved in transcriptional regulation and are regulated by ligands. Haem functions as a ligand for REV-ERBs, whereas sterols (cholesterol, cholesterol sulphate and various oxysterols) function as ligands for RORs. Both classes of receptors recognize a similar DNA response element, typically denoted as a ROR response element. ROR activates transcription (via recruitment of transcriptional co-activators), whereas REV-ERB silences transcription (via recruitment of transcriptional co-repressors). REV-ERB functions as a ligand-dependent transcriptional repressor (haem binding is required for the recruitment of the co-repressor and transcriptional repression), whereas ROR typically functions as a constitutive activator of transcription, and the binding of oxysterol ligands results in decreased activity. AF1, activation function 1; DBD, DNA-binding domain; LBD, ligand-binding domain.