NR1D1 (REV-ERBA) binds to the same site in the promoter of the BMAL1 (ARNTL) gene as ROR-alpha (RORA). Whereas ROR-alpha activates transcription of BMAL1, REV-ERBA bound to heme recruits corepressors (NCoR and HDAC3) and inhibits transcription of BMAL1. Both REV-ERBA and ROR-alpha genes are targets of BMAL1:CLOCK/NPAS2 transactivation and they show alternating patterns of maximum protein levels, thus they give BMAL1 transcription circadian expression.
As inferred from mouse, RORA binds RRE DNA elements and recruits the coactivators PGC-1alpha (PPARGC1A), p300 (EP300, a histone acetylase), and NRIP1. Activation of BMAL1 (ARNTL) expression by ROR-alpha (RORA) is inferred from mouse. In mouse, Rora together with coactivators Ep300 and Ppargc1a bind the promoter of Bmal1 and activate transcription.
The ARNTL (BMAL1) gene is transcribed to yield mRNA and the mRNA is translated to yield ARNTL protein (Hogenesch et al. 1997, Ikeda et al. 1997, also inferred from mouse homologs). The ROR-alpha transcription factor binds the RORE element of the BMAL1 (ARNTL) promoter and activates transcription of the BMAL1 gene. The REV-ERBA transcription factor binds the same RORE element and represses transcription of the BMAL1 gene.