The heterodimeric transcription factor BMAL1:CLOCK1 promotes the expression of PER and CRY proteins. The PER:CRY protein complex in turn represses BMAL1:CLOCK-dependent transcriptional activation of PER and CRY promotors. BMAL1/CLOCK also activates the expression of ROR and REV-ERB (NR1D1 and NR1D2) proteins. These confer additional control as ROR competitively activates BMAL1 expression and REV-ERB proteins competitively inhibit BMAL1 expression. Created in BioRender.