Role of Rev-erbα domains for transactivation of the connexin43 promoter with Sp1

Rev-erbα, a component of the circadian clock, has also been known as a nuclear receptor that lacks activation function domain 2, functioning as a ligand-dependent transcriptional repressor. However, we recently reported that Rev-erbα activates connexin43 transcription by forming a complex with Sp1. Here we show that heme, a REV-ERB ligand, is dispensable for this novel mechanism and that Rev-erbβ, having homologies with Rev-erbα, does not activate connexin43, but competes with the Rev-erbα/Sp1. The A/B region of Rev-erbα, which is not conserved in Rev-erbβ, is a crucial activating domain, while the ligand binding domain, conserved in Rev-erbβ, functions as a competitor.

► Ligand is dispensable for transactivation of connexin43 by Rev-erbα/Sp1 complex.
► Rev-erbβ competes with the Rev-erbα/Sp1 complex.
► The A/B region of Rev-erbα, not conserved in Rev-erbβ, is an activating domain.
► The ligand biding domain of Rev-erbα, conserved in Rev-erbβ, acts as a competitor.