Functional organization of the GluR1 glutamate receptor promoter

The GluR1 glutamate receptor subunit is expressed in most brain areas and plays a major role in excitatory synaptic transmission. We cloned and sequenced 5 kilobase pairs of the rat GluR1 promoter and identified multiple transcriptional start sites between -295 and -202 (relative to the first ATG). Similar to other glutamate receptor subunit promoters, the GluR1 promoter lacks TATA and CAAT elements in that region but binds Sp1 proteins at two sites. Promoter activity of GluR1 fragments cloned into pGL3 was assessed by immunocytochemistry and by measuring luciferase activity after transfection into primary cultures of rat cortical neurons and glia. GluR1 promoter activity was stronger in neurons, with neuronal specificity appearing to reside mainly within the neuronal expression-enhancing regions, -1395 to -743 and -253 to -48. The latter region contains 4 sites that bound recombinant cAMP-response element-binding proteins and a glial silencing region between -253 and -202. In both neurons and glia, promoter activity was increased by a 64-base pair GA repeat upstream of the initiation sites and reduced by a 57-base pair region that contained an N box. In contrast to the GluR2 promoter the regulatory regions are mainly located outside of the GluR1 initiation region.