TISSUE-SPECIFIC TRANSCRIPTION OF THE RAT TYROSINE-HYDROXYLASE GENE REQUIRES SYNERGY BETWEEN AN AP-1 MOTIF AND AN OVERLAPPING E-BOX CONTAINING DYAD

被引:160
作者
YOON, SO [1 ]
CHIKARAISHI, DM [1 ]
机构
[1] TUFTS UNIV, SCH MED, NEUROSCI PROGRAM, BOSTON, MA 02111 USA
关键词
D O I
10.1016/0896-6273(92)90220-8
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Transcription of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, is regulated in a tissue-specific manner. We have identified sequences from -205 to -182 as the minimal enhancer for TH in pheochromocytoma cells using site-directed mutagenesis. This segment (TGATTCAGAGGCAGGTG-CCTGTGA) is composed of an AP-1 motif (TGATTCA) and an overlapping 20 bp dyad whose core resembles an E box site (CANNTG). Interaction between the two elements is necessary both in vivo and in vitro: mutation of either element caused a 65%-95% reduction in transcription, and the combination of the two elements conferred cell-specific activation on a heterologous promoter; separation of the two elements by an additional helical turn not only disrupted a DNA-protein complex unique to the two elements, but also abolished expression in vivo. Therefore, we conclude that the interaction between the AP-1 and the E box dyad motifs is responsible for cell-specific TH expression.
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页码:55 / 67
页数:13
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