Motifs resembling hepatocyte nuclear factor 1 and activator protein 3 mediate the tissue specificity of the human plasminogen gene

Germana Meroni, Giorgio Buraggi, Roberto Mantovani, Roberto Taramelli

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Plasminogen is one of the key elements in the fibrinolytic process. Like most of the gene products that participate in such reactions and which interact with plasminogen, the site of its synthesis is mainly confined to the hepatocyte. Plasminogen RNA has additionally been detected in kidney and very low amounts also in testes. Deletional analysis has indicated that two 5' sequences located within 2.5 kb of the first ATG are responsible for the transcriptional activation and the tissue specificity of the expression of the gene. By DNase protection and gel mobility shift assays with HepG2 nuclear extracts, the two sequences were localized and found to be the recognition sites for the widely known hepatocyte nuclear factor 1 (HNF-1) a trans-acting factor, and a nuclear factor like activator protein 3 (AP-3). The first one lies in a rather unusual position, i.e. within the 5'-untranslated region. The latter is located further upstream in a region between -2200 and -2100 from the plasminogen mRNA cap site. Moreover, site-directed mutagenesis coupled by functional experiments in HepG2 cells has demonstrated a synergism between these two positively acting elements in controlling the transcription of the human plasminogen gene.

Original languageEnglish
Pages (from-to)373-382
Number of pages10
JournalEuropean Journal of Biochemistry
Volume236
Issue number2
Publication statusPublished - 1996

Fingerprint

Hepatocyte Nuclear Factor 1
Organ Specificity
Plasminogen
Genes
Tissue
Mutagenesis
Trans-Activators
Deoxyribonucleases
5' Untranslated Regions
Hep G2 Cells
Electrophoretic Mobility Shift Assay
Transcription
Site-Directed Mutagenesis
Transcriptional Activation
Testis
Hepatocytes
Assays
Gels
Chemical activation
enhancer-binding protein AP-3

Keywords

  • apoprotein(a)
  • gene cluster
  • plasminogen
  • promoter
  • trans-acting factors

ASJC Scopus subject areas

  • Biochemistry

Cite this

Motifs resembling hepatocyte nuclear factor 1 and activator protein 3 mediate the tissue specificity of the human plasminogen gene. / Meroni, Germana; Buraggi, Giorgio; Mantovani, Roberto; Taramelli, Roberto.

In: European Journal of Biochemistry, Vol. 236, No. 2, 1996, p. 373-382.

Research output: Contribution to journalArticle

Meroni, Germana ; Buraggi, Giorgio ; Mantovani, Roberto ; Taramelli, Roberto. / Motifs resembling hepatocyte nuclear factor 1 and activator protein 3 mediate the tissue specificity of the human plasminogen gene. In: European Journal of Biochemistry. 1996 ; Vol. 236, No. 2. pp. 373-382.
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