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Regulation of tyrosine hydroxylase gene expression by retinoic acid receptor
Author(s) -
Jeong Hyerhan,
Kim MiSoo,
Kim SungWoo,
Kim KwangSoo,
Seol Wongi
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03866.x
Subject(s) - retinoic acid , tyrosine hydroxylase , biology , microbiology and biotechnology , transcription factor , retinoic acid receptor , reporter gene , electrophoretic mobility shift assay , gene expression , transcription (linguistics) , response element , gene , regulation of gene expression , promoter , biochemistry , enzyme , linguistics , philosophy
Retinoic acid (RA), a derivative of vitamin A, critically controls brain patterning and neurogenesis during embryogenesis, and is known to regulate morphological differentiation of catecholaminergic neuronal cells. In this study, we investigated whether the retinoic acid receptor (RAR), a transcription factor specifically activated by all‐ trans ‐RA, could directly regulate transcription of tyrosine hydroxylase ( TH ), the first and rate‐limiting step in the catecholamine biosynthesis pathway. First, treating TH‐expressing human neuroblastoma SK‐N‐BE(2)C cells with all‐ trans RA resulted in an approximately 1.7‐fold increase in endogenous TH mRNA expression, as determined by real‐time PCR analysis. Second, when SK‐N‐BE(2)C cells were transiently co‐transfected with the TH promoter‐luciferase reporter construct, reporter gene expression was prominently activated by RAR in a ligand‐dependent manner. Third, we identified a putative RAR responsive cis ‐regulatory element at − 1500 to − 1487 bp in the TH upstream promoter region by deletional and site‐directed mutational analysis. Finally, we demonstrated that this putative motif directly interacts with RAR protein in a sequence‐specific manner by means of an electrophoretic mobility shift assay. Taken together, our results indicate that the TH gene may be a direct downstream target of the RA signaling pathway and that RAR is able to activate TH transcription through interaction with an upstream sequence motif residing at − 1500 to − 1487 bp.