Cell type-specific expression of the Kv3.1 gene is mediated by a negative element in the 5 ' untranslated region of the Kv3.1 promoter

The Kv3.1 potassium channel gene is restrictively expressed in the CNS, and its expression level is especially high in neurons that are able to follow synaptic inputs at high frequencies. To understand the transcriptional mec hanisms controlling Kv3.1 expression, we have conducted a functional analys is of the Kv3.1 promoter in various cell lines of different tissue origins and in transgenic mice. Our results suggest that an upstream regulatory fra gment coupled with the 5' untranslated region (UTR) is able to confer tissu e-specific expression in both cell lines and in transgenic mice. Deletion a nalysis of the regulatory region carried out in cell lines reveals that a s trong negatively acting element, uniquely residing in the 5' UTR (+350 to 158), appears able to confer cell type specificity on both the Kv3.1 promot er and the thymidine kinase promoter in transient transfection assays. A we ak cell type-specific enhancer in the proximal region of the promoter (-123 to -71) also contributes to cell type-specific expression of the Kv3.1 gen e.