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BMAL1 and CLOCK are transcription factors that heterodimerize and bind to E-box element-containing promoters, including promoters for Per and Cry. PER and CRY form a complex that inhibits BMAL1/CLOCK. In an interlocked loop, BMAL1 and CLOCK target nuclear receptors, REV-ERB and ROR, which feedback to negatively or positively regulate BMAL1 transcription respectively
