Cross-talk among RORα1 and the Rev-erb family of orphan nuclear receptors

We have cloned Rev-erbβ, a novel isoform of the Rev-erbα orphan nuclear receptor. The DNA binding domains of Rev-erbα and β are highly related to each other and to the retinoic acid related orphan receptor (ROR)/RZR subfamily of nuclear receptors. Indeed, we find that all three receptors bind as monomers to the sequence AATGT-AGGTCA. Whereas RORα1 constitutively activates transcription through this sequence, both isoforms of Rev-erb are inactive. When coexpressed, both Rev-erb isoforms suppress the transcriptional activity of RORα1. Our data define Rev-erb and ROR/RZR as a family of related receptors with opposing activities on overlapping regulatory networks.