Jg. Jiang et al., The repressive function of AP2 transcription factor on the hepatocyte growth factor gene promoter, BIOC BIOP R, 272(3), 2000, pp. 882-886
Citations number
39
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Hepatocyte growth factor is an important multifunctional growth factor whos
e gene expression is tightly regulated at the transcriptional level. Previo
us studies from our laboratory have shown that several cis-acting elements
are present in the promoter and proximal promoter region of the HGF gene. I
n this study, we have uncovered that AP2 transcription factor specifically
binds to a regulatory site located at -230 to -260 in the upstream region o
f the HGF gene promoter. Gelshift and supershift assays confirmed that AP2
has high binding affinity to this region. Functional studies which introduc
ed a mutation in the AP2 core binding region as well as cotransfection expe
riments using an AP2 expression vector revealed that AP2 exerts a repressiv
e role on the HGF gene promoter activity. The AP2 binding site overlaps wit
h those of NF1 and USF/E-box binding sites which we have recently shown to
constitute a composite multifunctional docking site for the members of the
NF1 and USF transcription factor families. An inverse correlation was noted
between AP2 binding activity to this composite site and HGF gene expressio
n in different cell lines. Therefore, APS-mediated repression of the HGF ge
ne promoter may be part of the molecular mechanism responsible for regulati
ng HGF expression. (C) 2000 Academic Press.