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Within an interacting feed-back loop, CLOCK-BMAL1 complexes activate expression of nuclear receptors, REV-ERB α and RORα. Their protein products feedback to manage BMAL1 by competitively binding retinoic acid-related orphan receptor reaction factors in the BMAL1 promoter40. REV-ERBs repress the transcription of BMAL1, Whilst RORs activate it. The