Both the basal and inducible transcription of the tyrosine hydroxylase gene are dependent upon a cAMP response element.
The cAMP response element (CRE) mediates cAMP responsiveness in many eukaryotic genes (Roesler, W. J., Vandenbark, G. R., and Hansen, R. W. (1988) J. Biol. Chem. 263, 9063-9066). The tyrosine hydroxylase gene (TH) contains a single copy of a consensus CRE at -45 to -38 base pair (bp) upstream of the transcription initiation site. Deletional and mutational analyses of the upstream 2400-base pair region of the rat TH gene using transient transfection assay demonstrated that the CRE was essential for both cAMP-mediated induction and basal transcription of the TH gene. Another domain between -365 and -151 bp, containing the AP1 site, contributed to transcription to a smaller degree. Thus, the CRE appears to play an important dual role as a basal promoter element and an inducible enhancer for TH transcription. Interactions between the DNA binding factors in nuclear extract and CRE-containing oligonucleotides were investigated by gel retardation and competition assays. Oligonucleotides corresponding to the CRE regions of the TH or somatostatin gene gave rise to a pair of distinct protein-DNA complexes with identical mobilities in the gel retardation assay, suggesting that similar nuclear factor(s) might bind to the CREs of the TH and somatostatin genes. This study emphasizes a fundamental role of the CRE in transcriptional activation of the TH gene in catecholaminergic cells.
Kim
K S
KS
Laboratory of Molecular Neurobiology, Cornell University Medical College, Burke Medical Research Institute, White Plains, New York 10605.
Lee
M K
MK
Carroll
J
J
Joh
T H
TH
D000818:Animals; D001483:Base Sequence; D017362:Cyclic AMP Response Element-Binding Protein; D004252:DNA Mutational Analysis; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016716:PC12 Cells; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D017384:Sequence Deletion; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
D017362:Cyclic AMP Response Element-Binding Protein; D009838:Oligodeoxyribonucleotides; D014446:Tyrosine 3-Monooxygenase