Functional organization of the GluR1 glutamate receptor promoter

The GluR1 glutamate receptor subunit is expressed in most brain areas and p lays a major role in excitatory synaptic transmission. We cloned and sequen ced 5 kilobase pairs of the rat GluR1 promoter and identified multiple tran scriptional start sites between -295 and -202 (relative to the first ATG). Similar to other glutamate receptor subunit promoters, the GluR1 promoter l acks TATA and CAAT elements in that region but binds Spl proteins at two si tes. 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 act ivity was stronger in neurons, with neuronal specificity appearing to resid e mainly within the neuronal expression-enhancing regions, -1395 to -743 an d -253 to -48. The latter region contains 4 sites that bound recombinant cA MP-response element-binding proteins and a glial silencing region between - 253 and -202. In both neurons and dia, promoter activity was increased by a 64-base pair GA repeat upstream of the initiation sites and reduced by a 5 7-base pair region that contained an N box. In contrast to the GluR2 promot er the regulatory regions are mainly located outside of the GluR1 initiatio n region.