Excitotoxic brain lesion modifies binding to a USF binding site acting as a negative regulatory element in the Protease nexin-1 promoter

• Published in: Molecular and cellular neuroscience Vol. 8; no. 1; pp. 28 - 37
• Main Authors: Ernø, H, Küry, P, Nitsch, C, Jost, J P, Monard, D
• Format: Journal Article
• Language: English
• Published: United States 1996
• Subjects: Amyloid beta-Protein Precursor; Animals; Antibody Specificity; Astrocytes - chemistry; Astrocytes - enzymology; Base Sequence; Binding Sites - genetics; Carrier Proteins - chemistry; Carrier Proteins - genetics; Carrier Proteins - metabolism; Caudate Nucleus - chemistry; Caudate Nucleus - cytology; Caudate Nucleus - enzymology; Cells, Cultured - chemistry; Cells, Cultured - enzymology; Cerebral Cortex - cytology; DNA-Binding Proteins; Excitatory Amino Acid Agonists; Gene Expression Regulation - physiology; Helix-Loop-Helix Motifs - physiology; Ibotenic Acid; Male; Molecular Sequence Data; Mutagenesis - physiology; Neurotoxins; Promoter Regions, Genetic - physiology; Protease Nexins; Protein Binding - physiology; Putamen - chemistry; Putamen - cytology; Putamen - enzymology; Rats; Rats, Wistar; Receptors, Cell Surface; Repressor Proteins - immunology; Repressor Proteins - metabolism; Serpin E2; Transcription Factors - metabolism; Upstream Stimulatory Factors
• ISSN: 1044-7431
• DOI: 10.1006/mcne.1996.0041

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 shown by the missing nucleoside technique to be a CACGTG site (E-box) in the proximal part of the PN-1 promoter. The factor binding to this site is specifically recognized by antibodies directed against the human upstream 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/reporter construct together with an expression vector for human USF1 confirms the negative regulatory function of this site. Finally, we show that the binding to this USF site changed after ibotenic acid-induced lesion of the caudate putamen in the rat brain.