The Orphan Nuclear Receptor Rev-erbα Recruits the N-CoR/Histone Deacetylase 3 Corepressor to Regulate the Circadian Bmal1 Gene

Rev-erbalpha represses the activity of the mouse Bmal1 gene promoter.

• The repression of Bmal1 expression is linked to the levels of Rev-erbalpha mRNA.
• Rev-erbalpha binds directly to two conserved sites on the Bmal1 promoter, which are necessary for its repressive function.
• Binding of Rev-erbalpha recruits the N-CoR/HDAC3 complex, leading to decreased histone acetylation at the Bmal1 promoter.
• In human HepG2 liver cells, a reduction in HDAC3 levels results in increased Bmal1 mRNA expression.
• The N-CoR/HDAC3 complex is identified as a corepressor for Rev-erbalpha, influencing circadian rhythm gene expression.

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