The IR-1 at −291/−279 is required for 9cRA-, but not for CDCA-mediated induction of the human SHP promoter.

DLD-1 cells were transfected with hFXR and hRXRα expression plasmids and various hSHP promoter constructs as indicated. Cells were treated with or without 100 µmol/L CDCA and/or 1 µmol/L 9cRA. The synergistic effect of the FXR ligand (CDCA) and RXRα ligand (9cRA) on SHP promoter activity depends on the previously identified IR-1 located at −291/−279. Mutation or deletion of this IR-1 sequence did not abolish SHP promoter activation by FXR/CDCA. Luciferase activity was measured to determine the SHP promoter activity. Data are presented as means ± SD; n≥3. Vehicle-treated conditions are set to 1. p≤0.05 for *) in a pairwise comparison by Mann-Whitney U test.