COACTIVATORS AND CO-REPRESSORS IN THE INTEGRATION OF TRANSCRIPTIONAL RESPONSES

The nuclear hormone receptors are DNA binding transcription factors th at are regulated by binding of ligands, switching them from an inactiv e or repressive state to gene-activating functions. Recent evidence su pports the hypothesis that many nuclear receptors switch, in a ligand- dependent manner, between binding of a multicomponent cc-repressor com plex containing histone deacetyltransferase activity, and binding of a cc-activator complex containing factors with histone acetyltransferas e activity that are further regulated by diverse signal transduction p athways. The identification of these limiting cc-repressor and cc-acti vator complexes and their specific interaction motifs, in concert with solution of the structures of the receptor ligand-binding domain in a po (empty) and ligand bound forms, indicates a common molecular mechan ism by which these factors activate and repress gene transcription.