TY - JOUR
T1 - Tissue-specific transcription of the rat tyrosine hydroxylase gene requires synergy between an AP-1 motif and an overlapping E box-containing dyad
AU - Yoon, Sung Ok
AU - Chikaraishi, Dona M.
N1 - Funding Information:
We are grateful to Dr. D. D. Hunter, Dr. C. Moore, and Dr. J. Wang for their critical comments on the manucript. This work was supported by grant NS22675 from the National Institutes of Health to D. M. C. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 USC Section 1734 solely to indicate this fact.
PY - 1992/7
Y1 - 1992/7
N2 - Transcription of tyrosine hydroxylase (TH), the ratelimiting 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 by 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.
AB - Transcription of tyrosine hydroxylase (TH), the ratelimiting 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 by 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.
UR - https://www.scopus.com/pages/publications/0026703977
U2 - 10.1016/0896-6273(92)90220-8
DO - 10.1016/0896-6273(92)90220-8
M3 - Article
C2 - 1352985
AN - SCOPUS:0026703977
SN - 0896-6273
VL - 9
SP - 55
EP - 67
JO - Neuron
JF - Neuron
IS - 1
ER -