The orphan receptor Rev-erbα gene is a target of the circadian clock pacemaker

Rev-erbalpha mRNA isoforms exhibit a circadian expression pattern and are regulated by the CLOCK-BMAL1 complex.

• Two mRNA isoforms of Rev-erbalpha, Rev-erbalpha1 and Rev-erbalpha2, are produced through different promoters.
• Both isoforms show a circadian expression pattern in fibroblasts.
• The CLOCK-BMAL1 complex activates both promoters by 3-6-fold.
• Overexpression of CRY1 inhibits the activation of these promoters.
• Regulation of Rev-erbalpha by CLOCK is conserved across vertebrates, including zebrafish.
• Circadian expression of Rev-erbalpha is significantly impaired in Clock mutant mice and zebrafish embryos treated with specific antisense oligonucleotides.

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