A FUNCTIONAL REV-ERB-ALPHA RESPONSIVE ELEMENT LOCATED IN THE HUMAN REV-ERB-ALPHA PROMOTER MEDIATES A REPRESSING ACTIVITY

Rev-erb alpha belongs to the nuclear receptor superfamily, which conta ins receptors for steroids, thyroid hormones, retinoic acid, and vitam in D, as well as ''orphan'' receptors, No ligand has been found for Re v-erb alpha to date, making it one of these orphan receptors, Similar to some other orphan receptors, Rev-erb alpha has been shown to bind D NA as a monomer on a specific sequence called a Rev-erb alpha responsi ve element (RevRE), but its transcriptional activity remains unclear, In this paper, we characterize a functional RevRE located in the human Rev-erb alpha promoter itself, We also present evidence that (i) Rev- erb alpha mediates transcriptional repression of its own promoter in v itro, (ii) this repressing effect strictly depends on the binding of R ev-erb alpha to its responsive element and is transferable to a hetero logous promoter; and (iii) Rev-erb alpha binds to this responsive sequ ence as a homodimer.