Differential effects of heterogeneous nuclear ribonucleoprotein K on Sp1- and Sp3-mediated transcriptional activation of a neuronal nicotinic 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, those encoding the alpha 3, alpha 5, and beta 4 subunits, are clustered tightly within the genome. These three subunits constitute the predominant acetylcholine receptor subtype expressed in the peripheral nervous system. The genomic proximity of the three genes suggests a regulatory mechanism ensuring their coordinate expression. However, it is likely that gene-specific regulatory mechanisms are also functioning because the expression patterns of the three genes, although similar, are not identical. Previously we identified regulatory elements within the beta 4 promoter region and demonstrated that these elements interact specifically with nuclear proteins. One of these elements, E1, interacts with the regulatory factor Pur alpha as well as three other unidentified DNA-binding proteins with. molecular masses of 31, 65, and 114 kDa, Another element, E2, interacts with Spl and Sp3, Because El and E2 are immediately adjacent to one another, we postulated that the proteins that bind to the elements interact to regulate beta 4 gene expression. Here we report the identification of the 65-kDa El-binding protein as heterogeneous nuclear ribonucleoprotein K and demonstrate that it affects the transactivation of beta 4 promoter activity by Spl and Sp3 differentially.