REV-ERBA binds DNA elements very similar to those bound by the transcription activator RORA. RORAREV-ERBA bound to DNA and heme recruits the corepressors NCoR and HDAC3 to repress transcription. Thus REV-ERBA and RORA appear to compete to repress or activate genes, repectively.
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Yin L, Wu N, Lazar MA.; ''Nuclear receptor Rev-erbalpha: a heme receptor that coordinates circadian rhythm and metabolism.''; PubMedEurope PMCScholia
Phelan CA, Gampe RT, Lambert MH, Parks DJ, Montana V, Bynum J, Broderick TM, Hu X, Williams SP, Nolte RT, Lazar MA.; ''Structure of Rev-erbalpha bound to N-CoR reveals a unique mechanism of nuclear receptor-co-repressor interaction.''; PubMedEurope PMCScholia
Raghuram S, Stayrook KR, Huang P, Rogers PM, Nosie AK, McClure DB, Burris LL, Khorasanizadeh S, Burris TP, Rastinejad F.; ''Identification of heme as the ligand for the orphan nuclear receptors REV-ERBalpha and REV-ERBbeta.''; PubMedEurope PMCScholia
Yin L, Wu N, Curtin JC, Qatanani M, Szwergold NR, Reid RA, Waitt GM, Parks DJ, Pearce KH, Wisely GB, Lazar MA.; ''Rev-erbalpha, a heme sensor that coordinates metabolic and circadian pathways.''; PubMedEurope PMCScholia
NR1D1 (REV-ERBA) binds heme. The NR1D1:heme complex is then able to recruit the corepressors NCoR and HDAC3. Corepressors do not bind NR1D1 in the absence of heme. NR1D1:heme binds a RRE element in the promoter of the ARNTL (BMAL1) gene, recruits corepressors, and represses transcription.
NR1D1 (REV-ERBA) binds the promoter of the NPAS2 gene and recruits corepressors to repress transcription. Recruitment of repressors appears to depend on the binding of heme by NR1D1.
As inferred from mouse homologs, REV-ERBA (NR1D1) binds the promoter of the ELOVL3 gene and represses transcription, possibly by recruiting corepressors.
NR1D1 (REV-ERBA) binds heme and the promoter of the PGC-1alpha (PPARGC1A) gene. The REV-ERBA:heme complex recruits the corepressors NCoR and HDAC3 and represses transcription.
NR1D1 (REV-ERBA) binds the promoter of the CLOCK gene and recruits corepressors to repress transcription. Recruitment of repressors appears to depend on the binding of heme by NR1D1.
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