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Nucleic Acids Research, 1988, Vol. 16, No. 7 2805-2824
© 1988

Articles

The regulatory region of the human plasminogen activator inhibitor type-1 (PAI-1) gene

Andrea Riccio1,2,*, Leif Røge Lund3, Renata Sartorio1,+, Arturo Lania1, Peter A. Anderasen3,4, Keld Danø3 and Francesco Blasi1,2

1International Institute of Genetics and Biophysics, CNR via Marconi, 10, 80125 Napoli, Italy 2Institute of Microbiology, University of Copenhagen Øster Farimagsgade 2A, 1353 Copenhagen K 3Finsen Laboratory, Rigshospitalet Strandboulevarden 49, 2100 Copenhagen Ø 4Institute of Biochemistry C, University of Copenhagen Blegdamsvej 3C, 2200 Copenhagen, Denmark

*To whom corresponence should be addressed

Received January 12, 1988. Revised March 8, 1988. Accepted March 8, 1988.

The human gene for plasminogen activator inhibitor type-1 (PAI-1) has been isolated and its promoter region characterized. PAI-1 regulation by glucocortiooids, transforming growth factor-ß (TGF-ß) and the phorbol ester PMA is shown to be exerted at the promoter level. A fragment spanning 805 nuclectides of the 5' flanking and 72 of the 5' untraslated region contain information enough to promote transcription and to respond to glucocorticoids when fused to a reporter gene and transfected into human fibrosarccma cells. A moderately repectitive DNA sequence, containing a TATA box, a GRE consensus, a Z-DNA forming sequence and two imperfect direct repeats at the extremities, is present a few nucleotides 5' of the human PAI-1 gene transcription start site, raising the possiblity that this gene could have been activated by DNA insertion during evolution.

+On leave from Department of Pediatrics, 2nd Medical School, University of Napoli, via Pansini 5, 80131 Napoli, Italy


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