Promoter context- and response element-dependent specificity of the transcriptional activation and modulating functions of retinoic acid receptors.

Using several naturally occurring and synthetic retinoic acid (RA)-responsive reporter genes, we show that the patterns of transcriptional activation by various retinoic acid receptor (RAR) and retinoid X receptor (RXR) forms vary according to the nature of the RA response element and the context of the stimulated promoter. We demonstrate the presence of autonomous, ligand-inducible, and promoter context-dependent transactivation functions (AF-2s) located in the C-terminal region of all RARs and RXRs. In addition, promoter context-specific modulating transactivation functions are associated with the N-terminal A and B regions of RARs and RXRs. We also show that these transactivation and modulating functions exhibit response-element specificity. The modulating functions display a marked specificity in their cooperation with the AF-2 transactivation functions, cooperation that depends on the receptor origin of the modulating and transactivation functions and the promoter context of the RA-responsive gene, thus accounting for the specific transactivation properties of RAR and RXR types.