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Titolo:
TRANSCRIPTIONAL REGULATION OF THE GLUR2 GENE - NEURAL-SPECIFIC EXPRESSION, MULTIPLE PROMOTERS, AND REGULATORY ELEMENTS
Autore:
MYERS SJ; PETERS J; HUANG YF; COMER MB; BARTHEL F; DINGLEDINE R;
Indirizzi:
EMORY UNIV,SCH MED,DEPT PHARMACOL ATLANTA GA 30322 UNIV N CAROLINA,DEPT PHARMACOL CHAPEL HILL NC 27599 UNIV BORDEAUX 2,INSERM,U259 F-33077 BORDEAUX FRANCE
Titolo Testata:
The Journal of neuroscience
fascicolo: 17, volume: 18, anno: 1998,
pagine: 6723 - 6739
SICI:
0270-6474(1998)18:17<6723:TROTGG>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
SODIUM-CHANNEL GENE; SELECTIVE GLUTAMATE RECEPTORS; RESTRICTIVE SILENCER FACTOR; CALCIUM-PERMEABLE AMPA; MESSENGER-RNAS; RAT-BRAIN; SUBUNIT COMPOSITION; CA2+ PERMEABILITY; INWARD RECTIFICATION; KAINATE RECEPTORS;
Keywords:
AMPA; GLUTAMATE RECEPTOR; TRANSCRIPTION; REST; NRF-1; PRIMARY CULTURE; TRANSFECTION; LUCIFERASE; NEURONS; PROMOTER; SP1; SILENCER; NEURONAL EXPRESSION; REPRESSOR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
71
Recensione:
Indirizzi per estratti:
Citazione:
S.J. Myers et al., "TRANSCRIPTIONAL REGULATION OF THE GLUR2 GENE - NEURAL-SPECIFIC EXPRESSION, MULTIPLE PROMOTERS, AND REGULATORY ELEMENTS", The Journal of neuroscience, 18(17), 1998, pp. 6723-6739

Abstract

To understand how neurons control the expression of the AMPA receptorsubunit GluR2, we cloned the 5' proximal region of the rat gene and investigated GluR2 promoter activity by transient transfection. RNase protection and primer extension of rat brain mRNA revealed multiple transcription initiation sites from -340 to -481 bases upstream of the GluR2 AUG codon. The relative use of 5' start sites was different in cortex and cerebellum, indicating complexity of GluR2 transcript expression among different sets of neurons. When GluR2 promoter activity was investigated by plasmid transfection into cultured cortical neurons, cortical glia, and C6 glioma cells, the promoter construct with the strongest activity, per transfected cell, was 29.4-fold (+/- 3.7) more active in neurons than in non-neural cells. Immunostaining of cortical cultures showed that >97% of the luciferase-positive cells also expressed the neuronal marker MAP-2. Evaluation of internal deletion and substitution mutations identified a functional repressor element I RE1-likesilencer and functional Sp1 and nuclear respiratory factor-1 (NRF-1) elements within a GC-rich proximal GluR2 promoter region. The GluR2 silencer reduced promoter activity in glia and non-neuronal cell lines by two- to threefold, was without effect in cortical neurons, and couldbind the RE1-silencing transcription factor (REST) because cotransfection of REST into neurons reduced GluR2 promoter activity in a silencer-dependent manner. Substitution of the GluR2 silencer by the homologous Nail REI silencer further reduced GluR2 promoter activity in nonneuronal cells by 30-47%. Maximal positive GluR2 promoter activity required both Spl and NRF-1 cis elements and an interelement nucleotide bridge sequence. These results indicate that GluR2 transcription initiatesfrom multiple sites, is highly neuronal selective, and is regulated by three regulatory elements in the 5' proximal promoter region.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 09:12:40