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Titolo:
Analysis of the 5 '-flanking region of the beta-amyloid precursor protein gene that contributes to increased promoter activity in differentiated neuronal cells
Autore:
Lahiri, DK; Song, WH; Ge, YW;
Indirizzi:
Indiana Univ, Sch Med, Dept Psychiat, Inst Psychiat Res,Lab Mol Neurogenet, Indianapolis, IN 46202 USA Indiana Univ Indianapolis IN USA 46202 ogenet, Indianapolis, IN 46202 USA Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA Indiana Univ Indianapolis IN USA 46202 Genet, Indianapolis, IN 46202 USA
Titolo Testata:
MOLECULAR BRAIN RESEARCH
fascicolo: 2, volume: 77, anno: 2000,
pagine: 185 - 198
SICI:
0169-328X(20000505)77:2<185:AOT5'R>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
NERVE GROWTH-FACTOR; INTERLEUKIN-1 REGULATES SYNTHESIS; ALZHEIMERS-DISEASE; MESSENGER-RNA; PC12 CELLS; TRANSGENIC MICE; APP GENE; INCREASED EXPRESSION; PHORBOL ESTER; RAT-BRAIN;
Keywords:
Alzheimer's disease; beta-amyloid precursor protein; gene regulation; nerve growth factor; neuronal differentiation; PC12 cells; promoter; transfection;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
45
Recensione:
Indirizzi per estratti:
Indirizzo: Lahiri, DK Indiana Univ, Sch Med, Dept Psychiat, Inst Psychiat Res,Lab MolNeurogenet, 791 Union Dr,Room Pr313, Indianapolis, IN 46202 USA Indiana Univ 791 Union Dr,Room Pr313 Indianapolis IN USA 46202
Citazione:
D.K. Lahiri et al., "Analysis of the 5 '-flanking region of the beta-amyloid precursor protein gene that contributes to increased promoter activity in differentiated neuronal cells", MOL BRAIN R, 77(2), 2000, pp. 185-198

Abstract

To study the transcription control of the beta-amyloid precursor protein (beta APP) in Alzheimer's disease (AD), we functionally characterized the beta APP gene promoter in differentiated cells. PC12 cells were first differentiated with nerve growth factor (NGF) and then transient transfection analysis was done with a series of 5'-deletion constructs, that extended as farupstream as -7900 down to + 104 base pair (bp) relative to the transcription start site (+1). The truncated regions of the promoter were linked upstream to a reporter gene, chloramphenicol acetyl transferase (CAT). The CAT assay was performed to compare promoter activity of different 5'-fanking andintronic regions of the beta APP gene. Our results suggest that the longest (-7900/+104) and one of the shortest (-47/+104) regions possessed significantly higher levels of promoter activity than the promoterless vector in NGF-differentiated PC12 cells. A deletion of about 7600 bp region from the -7900 to +104 construct resulted in 50% loss of original promoter activity. A deletion of all but 47 bp from the -7900 to +104 construct resulted in the loss of 66% (and retention of 34%) promoter activity. The region -3416/+104 bp displayed the strongest promoter activity whereas +1/+104 bp showed the least activity among all deletion constructs studied. The upstream region -5529 to -3416 contains a negative regulatory element and -3416 to -1131 contains a positive regulatory element. The very upstream region, -7900 to -3411, lacks independent functional activity. The 5'-UTR region (+1 to +104) showed minimum activity and the -75 to +104 region constitutes the basic promoter element. The first exon or a large part of the first intron (+99 to +6200) did not display any significant promoter activity. Thus, several positive and negative regulatory elements influence the basal level of beta APP promoter activity in NGF-differentiated PC12 cells. We speculate that any structural alteration(s) due to a specific mutation in these regulatory regions can potentially alter the transcriptional machinery, and that can perhaps affect the level of beta-amyloid protein involved in AD. (C) 2000 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/04/20 alle ore 19:54:33