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The Journal of Neuroscience, November 15, 1999, 19(22):9747-9755

Cell Type-Specific Activation of Neuronal Nicotinic Acetylcholine Receptor Subunit Genes by Sox10

Qun Liu, Irena N. Melnikova, Minjie Hu, and Paul D. Gardner

Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, Texas 78245-3207

The regulatory factor Sox10 is expressed in neural crest derivatives during development as well as in the adult CNS and peripheral nervous system. Mutations of the human Sox10 gene have been identified in patients with Waardenburg-Hirschsprung syndrome that is characterized by defects in neural crest development. Previous studies suggested that Sox10 might function as an important transcriptional regulator of neural crest development. No natural target genes of Sox10 have yet been identified. Although human Sox10 activates a synthetic promoter consisting of a TATA box and multiple Sox consensus sequences, no transcriptional activity of the rat Sox10 homolog has been detected. Here we report that the neuronal nicotinic acetylcholine receptor 4 and 3 subunit gene promoters are transactivated by rat Sox10 in a cell type-specific manner. The 3 and 4 subunits, in combination with the 5 subunit, make up the predominant nicotinic receptor subtype expressed in the peripheral nervous system. Transfections using Sox10 mutants indicate that the C-terminal region is dispensable for its ability to activate the 4 and 3 promoters. Rat Sox10 was originally identified 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 3 promoter. We now demonstrate that it can transactivate the 4 promoter as well. However, we were unable to detect any synergistic effects of Sox10 and Tst-1/Oct6/SCIP on 4 or 3 promoter activity. Finally, we present data suggesting that recombinant Sox10 protein can directly interact with a previously characterized regulatory region of the 4 gene.

Key words: Sox10; gene expression; nACh receptor; ligand-gated ion channel; transcriptional regulation; POU

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Copyright © 1999 Society for Neuroscience  0270-6474/99/19229747-09$05.00/0

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