Bile acids and SHP decrease expression from the SREBP-1c promoter. (A) Expression of SREBP-1c and several of its target genes in mouse liver primary hepatocyte cultures. The presence of ligands for LXR (22(R)-hydroxycholesterol, 20 µM) and RXR (LG100268, 1 µM) is indicated by a + sign. FXR was activated by the addition of CDCA to the medium (50 µM and 200 µM). (B) Activity of the mouse SREBP-1c promoter in the McA-RH7777 cell line after the addition of 200 µM CDCA or 200 µM CA to the medium. Cells were tested in the absence or presence of cotransfected LXRα and ligands for RXR and LXR at the concentrations specified in A. (C) Schematic representation of the different constructs of the mouse SREBP-1c promoter used in transfection assays. Binding sites for LXR are displayed as ovals. The nucleotide numbering is relative to the SREBP-1c start codon. (D) Sequence comparison of the LXRREs in the human and mouse SREBP-1c promoters. The GenBank accession numbers for the human SREBP-1c promoter sequence are NT_010718 or AC122129. (E) Activity of the mSREBP-1c reporters in McA-RH7777 cells transfected either with an empty expression vector or with the indicated combinations of expression vectors for mouse LRH-1, mouse RXRα, human LXRα, mouse SHP in the presence (black bars) or absence (white bars) of LXR (22(R)-hydroxycholesterol; 20 µM) and RXR agonists (LG100268; 1 µM).