The hepatocyte nuclear factor 3beta stimulates the transcription of the human insulin-like growth factor I gene in a direct and indirect manner.
Promoter 1 (P1) of the human insulin-like growth factor I (IGF-I) gene is most active in adult liver. In this study we show that HNF-3beta, a member of the winged helix protein family of liver-enriched transcription factors, has a strong stimulatory effect on the activity of P1. Transient transfection experiments in combination with bandshift and DNase I footprinting analysis revealed the presence of two HNF-3 binding sites in the proximal promoter region of P1. Both binding sites, which are well conserved in evolution, are required for maximal transactivation. Studies employing HNF-3 mutant constructs indicated that IGF-I expression is also regulated indirectly by HNF-3beta as a consequence of enhanced expression of HNF-1alpha. This liver-enriched transcription factor has previously been shown to transactivate P1. Thus, HNF-3beta regulates the expression of the human IGF-I gene via two distinct mechanisms.
Nolten
L A
LA
Laboratory for Physiological Chemistry, Utrecht University, Graduate School of Developmental Biology, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands. steenbergh@med.ruu.nl
Steenbergh
P H
PH
Sussenbach
J S
JS
D000328:Adult; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D019556:COS Cells; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D051542:Hepatocyte Nuclear Factor 3-beta; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; C496502:FOXA2 protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; D051542:Hepatocyte Nuclear Factor 3-beta; D007334:Insulin-Like Growth Factor I