DIFFERENTIAL-EFFECTS OF HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN-K ON SP1-MEDIATED AND SP3-MEDIATED TRANSCRIPTIONAL ACTIVATION OF A NEURONALNICOTINIC ACETYLCHOLINE-RECEPTOR PROMOTER

The neuronal nicotinic acetylcholine receptor gene family consists of II members, alpha 2-alpha 9 and beta 2-beta 4, Three of the genes, tho se encoding the alpha 3, alpha 5, and beta 4 subunits, are clustered t ightly within the genome. These three subunits constitute the predomin ant acetylcholine receptor subtype expressed in the peripheral nervous system. The genomic proximity of the three genes suggests a regulator y mechanism ensuring their coordinate expression. However, it is likel y that gene-specific regulatory mechanisms are also functioning becaus e the expression patterns of the three genes, although similar, are no t identical. Previously we identified regulatory elements within the b eta 4 promoter region and demonstrated that these elements interact sp ecifically with nuclear proteins. One of these elements, E1, interacts with the regulatory factor Pur alpha as well as three other unidentif ied DNA-binding proteins with. molecular masses of 31, 65, and 114 kDa , Another element, E2, interacts with Spl and Sp3, Because El and E2 a re immediately adjacent to one another, we postulated that the protein s that bind to the elements interact to regulate beta 4 gene expressio n. Here we report the identification of the 65-kDa El-binding protein as heterogeneous nuclear ribonucleoprotein K and demonstrate that it a ffects the transactivation of beta 4 promoter activity by Spl and Sp3 differentially.