(A) The retinoic acid receptors, RXR and RARα, harbor distinct DNA-binding domains (DBD) and ligand-binding domains (LBD) and bind as a heterodimer to a specific direct repeat separated by 5 bp making up the retinoic acid response element (RARE). (B) In the absence of ligand, the RXR-RARα heterodimer associates with a transcriptional repressor complex, including N-CoR, mSin3a, and a histone deacetylase (HDAC-1). (C) The addition of all-trans retinoic acid (ATRA) results in a conformational change in the RXR-RAR heterodimer resulting in the release of the repressor complex and recruitment of a transcriptional activator complex exhibiting histone acetyltransferase activity and associated transcriptional activation.