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J Biol Chem, Vol. 273, Issue 31, 19877-19883, July 31, 1998

Differential Effects of Heterogeneous Nuclear Ribonucleoprotein K on Sp1- and Sp3-mediated Transcriptional Activation of a Neuronal Nicotinic Acetylcholine Receptor Promoter

From the Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center, San Antonio, Texas 78245-3207

The neuronal nicotinic acetylcholine receptor gene family consists of 11 members, 2-9 and 2-4. Three of the genes, those encoding the 3, 5, and 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 4 promoter region and demonstrated that these elements interact specifically with nuclear proteins. One of these elements, E1, interacts with the regulatory factor Pur as well as three other unidentified DNA-binding proteins with molecular masses of 31, 65, and 114 kDa. Another element, E2, interacts with Sp1 and Sp3. Because E1 and E2 are immediately adjacent to one another, we postulated that the proteins that bind to the elements interact to regulate 4 gene expression. Here we report the identification of the 65-kDa E1-binding protein as heterogeneous nuclear ribonucleoprotein K and demonstrate that it affects the transactivation of 4 promoter activity by Sp1 and Sp3 differentially.

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