Positive and negative elements modulate the promoter of the human liver- specific α2-HS-glycoprotein gene

Fatima Banine, Christophe Gangneux, Louis Mercier, Alphonse Le Cam, Jean Philippe Salier

    Research output: Contribution to journalArticle

    17 Scopus citations

    Abstract

    The human α2-HS-glycoprotein (AHSG) and the 63-kDa rat phosphoprotein (pp63) are homologous plasma proteins that belong to the fetuin family. AHSG and pp63 are involved in important functions such as inhibition of insulin receptor tyrosine kinase activity, inhibition of protease activities, and regulation of calcium metabolism and osteogenesis. Studies of the AHSG proximal promoter performed in vitro in rat and human cells indicate that several NF-1 and C/EBP binding sites exert a positive effect on its transcriptional activity. However, until now, no distal elements have been examined in this gene, in either species. We report that the human AHSG gene promoter acts in a liver-specific manner and is further controlled by three distal, 5'-flanking elements. The negative elements III and I are, respectively, located 5' and 3' of the positive element II. All three elements require the natural context of the human AHSG gene to fully exert their negative or positive effect. Element I harbours a single binding site for NF-1. This nuclear factor thus appears to be able to up- or downregulate the AHSG gene depending on the site it binds to. Elements I, II and possibly III are absent in the rodent Ahsg gene encoding pp63.

    Original languageEnglish (US)
    Pages (from-to)1214-1222
    Number of pages9
    JournalEuropean Journal of Biochemistry
    Volume267
    Issue number4
    DOIs
    StatePublished - Mar 4 2000

    Keywords

    • Hepatic transcription
    • NF-1
    • Promoter
    • Silencer
    • α2-HS-glycoprotein

    ASJC Scopus subject areas

    • Biochemistry

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