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Volume 17, Number 11, Issue of June 1, 1997 pp. 4076-4086
Copyright ©1997 Society for Neuroscience

A Novel Basal Promoter Element Is Required for Expression of the Rat Tyrosine Hydroxylase Gene

Received Oct. 21, 1996; revised Feb. 28, 1997; accepted March 19, 1997.

Swati Patankar¹, Meredith Lazaroff², Sung Ok Yoon¹, and Dona M. Chikaraishi^{1, 2}

Departments of ¹ Molecular Biology and Microbiology and ² Neuroscience, Tufts University School of Medicine, Boston, Massachusetts 02111

Transcription of the rat tyrosine hydroxylase (TH) gene is controlled by enhancer sequences in its 5 flanking region; these enhancers include the AP1, dyad, and cAMP response element (CRE) motifs. We show that a novel basal promoter element (17 GCCTGCCTGGCGA 5) positioned between the TATA box and +1 works in conjunction with the upstream AP1-dyad and CRE enhancers but cannot support transcription by itself. A mutation of this element, termed partial dyad, reduces basal expression of a reporter gene in TH-positive cell lines and TH-negative lines but has no effect on cAMP- or KCl-induced expression. A double mutant at positions 17 and 11 of the partial dyad reduces transcriptional activation by 80%. Conversely, insertion of this element into a heterologous promoter restores basal expression to levels mediated by the native TH promoter. The partial dyad is a novel activational element that is required for full expression of the TH gene and may assist in the function of the AP1, dyad, and CRE motifs and also other enhancers further upstream. Hence, the rat TH gene is unusual in that its enhancers will not function with a heterologous promoter but require a specific TH promoter sequence for full activation.

Key words: tyrosine hydroxylase; promoter; CRE; TATA box; AP1; cAMP; depolarization

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