Involvement of Sp1 in basal and retinoic acid induced transcription of thehuman tissue-type plasminogen activator gene

Transcription of the human tissue-type plasminogen activator (t-PA) gene is regulated by a multi-hormonal responsive enhancer at -7 kb, Transient co-t ransfections of Drosophila SL2 and human HT1080 fibrosarcoma cells with t-P A reporter constructs showed that Sp1 and Sp3 activate the t-PA promoter. M oreover Sp1 (but not Sp3) binding to the promoter is involved in induction by retinoic acid (RA), a response mediated through the enhancer. The role o f Sp1 is specific, since mutation of the CRE element in the promoter did no t affect response to RA, In contrast, the glucocorticoid induction mediated by the enhancer is independent of these Spl and CRE elements. (C) 1999 Fed eration of European Biochemical Societies.