Interactions between liver nuclear proteins and the human insulin-like growth factor binding protein 1 promoter in the course of development

Unite de Recherches sur la Regulation de la Croissance, INSERM U.142, Hopital Saint Antoine, Paris, France.

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, PC1 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-1 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-1 gene transcription.