TRANSCRIPTIONAL REGULATION OF THE alpha-FETOPROTEIN GENE IN HEPATOCYTES

摘要

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 a (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/EBPa, HNFla, NF-1 and coactivator p300 gave the maximal activity. Mutation in either HNFla 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, HNF1alpha, C/EBPalpha, NF-1, and p300 bound to the AFP promoter in adult liver.