CYTOSOLIC CALCIUM IS ESSENTIAL IN TBE BASAL EXPRESSION OF TYROSINE-HYDROXYLASE GENE

To test the role of cytosolic calcium in the basal expression of a neuronal gene, promoter activity of the rat tyrosine hydroxylase (TH) gene was monitored upon reduced resting level of intracellular calcium. TH promoter activity was decreased by cell-permeable calcium chelator, BAPTA/AM, in SK-N-BE(2)C human neuroblastoma cells. The cAMP response element (CRE) was mapped to the calcium responsible element by mutational and deletional analysis of the 5' upstream promoter region. Gel shift assay showed 2 CRE-specific DNA-protein complexes. The quantities of specific complexes were markedly decreased in BAPTA/AM-treated cells. These data suggest that resting level of intracellular calcium has a critical role in the basal expression of TH gene through the regulation of the binding of nuclear proteins to the CRE motif in the promoter. (C) 1995 Academic Press, Inc.