Potential regulation of hepatic FGF21 expression by p53 and STAT3. A : Luciferase reporter activities with different FGF21 promoter sequences. Potential p53 binding locus and sequence conservation in the proximal region of FGF21 promoter were shown across human, mouse and rat species. Reporter assays were performed in Hep3B cells co-transfected with the indicated FGF21-luciferase reporter plasmids (−1497, -443 and −97) or control plasmid (+5) in the absence (gray bar) or presence of expression plasmids for p53 wildtype (black bars) and mutant (open bar). Cells were maintained in high glucose medium. Data are shown as mean ± sd, * p < 0.05 (n = 3 for each data point). B : Determination of p53 and STAT3 binding regions. CHIP assay was performed as described in the Methods section in Hep3B cells. Antibody enrichment of DNA regions were analyzed by qPCR and expressed as percent recovery relative to the inputs. Normal IgG was used as negative control for p53 and active STAT3 antibodies. Values are means ± sd of duplicate PCRs performed at least three times with similar results, * p < 0.05.