Transcriptional regulation of the α-fetoprotein gene in hepatocytes

alpha-Fetoprotein (AFP) is a fetal serum protein enriched in fetal liver whose expression is downregulated during development. The proximal region of the AFP promoter contains two binding sites for CCAAT/enhancer-binding protein alpha (C/EBP alpha), two for hepatocyte nuclear factor-1 alpha (HNF1 alpha) and one for glucocorticoid receptor (GR) in addition to a nuclear factor-1 (NF-1) binding site, which partly overlaps with the distal C/EBPa binding site. Luciferase reporter assays showed that a combination of C/EBP alpha, HNF1 alpha, NF-1 and coactivator p300 gave the maximal activity. Mutation in either HNF1 alpha binding site diminished the expression completely but mutation in either or both of the C/EBPa binding sites did not severely reduce the expression level. Chromatin immunoprecipitation assays showed that GR, FINF1 alpha, C/EBP alpha, NF-1, and p300 bound to the AFP promoter in adult liver.