Cell type-specific activation of neuronal nicotinic acetylcholine receptorsubunit genes by Sox10

The regulatory factor Sox10 is expressed in neural crest derivatives during development as well as in the adult CNS and peripheral nervous system. Mut ations of the human Sox10 gene have been identified in patients with Waarde nburg-Hirschsprung syndrome that is characterized by defects in neural cres t development. Previous studies suggested that Sox10 might function as an i mportant transcriptional regulator of neural crest development. No natural target genes of Sox10 have yet been identified. Although human Sox10 activa tes a synthetic promoter consisting of a TATA box and multiple Sox consensu s sequences, no transcriptional activity of the rat Sox10 homolog has been detected. Here we report that the neuronal nicotinic acetylcholine receptor beta 4 and alpha 3 subunit gene promoters are transactivated by rat Sox10 in a cell type-specific manner. The alpha 3 and beta 4 subunits, in combina tion with the alpha 5 subunit, make up the predominant nicotinic receptor s ubtype expressed in the peripheral nervous system. Transfections using Sox1 0 mutants indicate that the C-terminal region is dispensable for its abilit y to activate the beta 4 and alpha 3 promoters. Rat Sox10 was originally id entified as an accessory protein of the POU domain protein Tst-1/Oct6/SCIP in glial cells. Tst-1/Oct6/SCIP was shown previously to activate the alpha 3 promoter. We now demonstrate that it can transactivate the beta 4 promote r as well. However, we were unable to detect any synergistic effects of Sox 10 and Tst-1/Oct6/SCIP on beta 4 or alpha 3 promoter activity. Finally, we present data suggesting that recombinant Sox10 protein can directly interac t with a previously characterized regulatory region of the beta 4 gene.