Rev-erbα and Rev-erbβ coordinately protect the circadian clock and normal metabolic function

Depletion of both Rev-erbα and Rev-erbβ leads to dramatic effects on the cell-autonomous clock and metabolism.

• Loss of both Rev-erbs causes mouse embryonic fibroblasts to become arrhythmic.
• In mouse livers, Rev-erbβ mRNA and protein levels show a diurnal pattern similar to Rev-erbα.
• Both Rev-erbs bind to a similar set of sites in the genome, particularly near metabolic genes.
• Depleting both Rev-erbs synergistically increases the activity of metabolic genes and genes that activate the molecular clock.
• Deficiency of both Rev-erbs results in significant hepatic steatosis, unlike the effects seen with the loss of either receptor alone.

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