EXCITOTOXIC BRAIN LESION MODIFIES BINDING TO A USF BINDING-SITE ACTING AS A NEGATIVE REGULATORY ELEMENT IN THE PROTEASE NEXIN-1 PROMOTER

The expression of the serine protease inhibitor Protease nexin-1 (PN-1 )is upregulated in glial cells following different types of lesion in the nervous system. A strong negative regulatory element has been show n by the missing nucleoside technique to be a CACGTG site (E-box) in t he proximal part of the PN-1 promoter. The factor binding to this site is specifically recognized by antibodies directed against the human u pstream stimulatory factor (USF). Point mutations in the E-box binding site which abolish USF binding in vitro increase the transcriptional activity of the PN-1 promoter. Cotransfection of a PN-1 promoter/repor ter construct together with an expression vector for human USF1 confir ms the negative regulatory function of this site. Finally, we show tha t the binding to this USF site changed after ibotenic acid-induced les ion of the caudate putamen in the rat brain.