Babajko S. Interactions between liver nuclear proteins and the human insulin-like growth factor binding protein 1 promoter in the course of development. Eur J Endocrinol 1995;132:635–41. ISSN 0804–4643
Insulin-like growth factor binding proteins (IGFBPs) modulate the bioavailability of the IGFs. Among the six IGFBPs known to date, IGFBP-1 is the most tissue-specific, its expression being limited to the liver and the endometrium. In the liver, IGFBP-1 gene expression is maximal during the perinatal period, with its peak corresponding to a transient rise in gene transcription activity. In this study, interactions between rat liver nuclear proteins and the human IGFBP-1 promoter have been analysed in the course of development, using in vitro DNase I protection and mobility shift assays. Only the interactions between DNA and proteins localized between nt –305 and –268 varied through the period studied (16 days in utero to 70 days postnatally). Three proteins, named Pa, PCI and PC2, interacted with sequences between nt –295 and –285, nt –305 and –295 and nt –285 and –268, respectively. There was a marked perinatal increase in phenotype expression of Pa, which was parallel to that in IGFBP-l gene transcription activity. In addition, DNA-Pa interactions and DNA-PC2 interactions were mutually exclusive. These results suggest that the interaction of Pa with its target sequence(s) prevent PC2 binding and thereby contribute towards increased IGFBP-l gene transcription.
Sylvie Babajko, INSERM U.142, Hôpital Saint Antoine, 184 rue du Faubourg St. Antoine, 75571 Paris Cedex 12, France