Fig. 3.

Direct binding of a distal enhancer of SHP by p53. (A) Schematic representation of a distal enhancer region of SHP with sequences similar to p53-response elements (RI), the promoter region containing FXR-response elements (RIII), and a nonspecific intervening region (RII). (B) A luciferase reporter driven by a minimal thymidine kinase promoter (TK) fused to five copies of SHP-p53REs, (RI)⁵-TK-LUC, but not the parental reporter with TK alone, TK-LUC, responded to p53 in a dose-dependent manner. (C) RT-PCR analysis of HepG2 cells treated with vehicle or DXR for 12 h to measure expression of p21, SHP, and cyclophilin A (control). (D–F) ChIP analysis of HepG2 cells (D and E) and mouse liver (F) treated with DXR for 2 h to examine the recruitment of p53 (D and F) and establishment of active chromatin (E). All experiments were repeated more than three times with similar results.