The Na-G ion channel is transcribed from a single promoter controlled by distinct neuron- and Schwann cell-specific DNA elements

Na-G is a putative sodium (or cationic) channel expressed in neurons and gl ia of the PNS, in restricted neuronal subpopulations of the brain, and in s everal tissues outside the nervous system, like lung and adrenal medulla. T o analyze the mechanisms underlying tissue-specific expression of this chan nel, we isolated the 5' region of the corresponding gene and show that Na-G mRNA transcription proceeds from a single promoter with multiple initiatio n sites. By transgenic mice studies, we demonstrate that 600 bp containing the Na-G proximal promoter region and the first exon are sufficient to driv e the expression of a beta-galactosidase reporter gene in neurons of both C NS and PNS, whereas expression in Schwann cells depends on more remote DNA elements lying in the region between -6,500 and -1,050 bp upstream of the m ain transcription initiation sites. Crucial elements for lung-specific expr ession seem to be located in the region between -1,050 and -375 bp upstream of the promoter. Using in vivo footprint experiments, we demonstrate that several sites of the Na-G proximal promoter region are bound specifically b y nuclear proteins in dorsal root ganglion neurons, as compared with nonexp ressing hepatoma cells.