Synergy between 5 ' and 3 ' flanking regions of the human tyrosine hydroxylase gene ensures specific, high-level expression in neuroblastoma cells

Factors regulating tyrosine hydroxylase (TH) gene transcription are of majo r importance in the studies of malignant and degenerative diseases of catec holamine-synthesizing tissues. In this study, we used transient transfectio n of a reporter gene to show that high-level, tissue-specific TH expression was only achieved when the reporter gene was cloned between a 5' TH promot er sequence (-513- + 1), and, a 3' TH gene flanking sequence tend of exon 1 4- + 976). We also show that TH mRNA expression level is closely linked to the expression level of the proto-oncogene, MYCN in neuroblastoma tumor cel l lines. Taken together our data indicate that MYCN may regulate TH express ion in neuroblastoma cells, but not through binding to the 5' or 3' TH gene flanking sequences used in our experiments. (C) 2000 Elsevier Science Irel and Ltd. All rights reserved.