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dc.contributor.author이영식-
dc.date.accessioned2021-01-07T04:54:43Z-
dc.date.available2021-01-07T04:54:43Z-
dc.date.issued2003-12-
dc.identifier.citationBIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v. 312, issue. 4, page. 1123-1131en_US
dc.identifier.issn0006-291X-
dc.identifier.issn1090-2104-
dc.identifier.urihttps://www.sciencedirect.com/science/article/pii/S0006291X0302360X-
dc.identifier.urihttps://repository.hanyang.ac.kr/handle/20.500.11754/156649-
dc.description.abstractTyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine biosynthesis, is predominantly expressed in several cell groups within the brain, including the dopaminergic (DA) neurons of the substantia nigra and ventral tegmental area, and the noradrenergic neurons of the locus coeruleus. To investigate the regulation of cell type-specific TH expression, we cloned and sequenced a 5.5kb fragment of human genomic DNA immediately 5′ of the TH coding region. This 5′-flanking region does not contain either a CAAT box or a GC-rich region, but does contain a TATA box and consensus binding sequences for basal (TATA and CRE), and DA neuron-specific (NBRE, Gli, and BBE) transcription factors. Sequence analysis showed low overall homology with the rat and mouse TH promoter regions, with the exception of two high-homology domains, which encompassed −2384 to −2323 and −123 to −65, respectively. Interestingly, these distal and proximal domains contained NBRE, BBE, CRE, and TATA boxes, which are known to play important roles in DA neurogenesis. To further localize the TH promoter region responsible for transcriptional activity, we fused a 3301-bp human TH promoter fragment (−3174 to +127) to a luciferase reporter gene, and used this to assess promoter activity in neuronal and non-neuronal cell lines. Consistent with endogenous TH expression, this promoter construct was active in SH-SY5Y human neuroblastoma cells but not F3 human neural stem cells (NSCs). Deletion analysis of TH promoter/luciferase constructs revealed the presence of the repressor element in −1232 to −1210 upstream of transcription initiation site. While this region repressed 85% of promoter activity when transfected into F3 cells, it was not active in SH-SY5Y cells. These data suggest that the repressor element may play an important role in neuron cell-specific expression of the TH gene. Our results may provide insight into neuronal cell-specific expression of the human TH gene and allow a better understanding of catecholaminergic neuron disorders such as Parkinson’s disease and schizophrenia.en_US
dc.description.sponsorshipThe research was supported by grants from the KOSEF/ BDRC Ajou University, Grant R03-2000-000-00012-0 from KOSEF, by a Neurobiology Research Program grant from the Korea Ministry of Science and Technology, and by Grant SC13072 from the Stem Cell Research Center of the 21st Century Frontier Research Program, funded by the Ministry of Science and Technology.en_US
dc.language.isoen_USen_US
dc.publisherACADEMIC PRESS INC ELSEVIER SCIENCEen_US
dc.subjectTyrosine hydroxylaseen_US
dc.subjectCloningen_US
dc.subjectPromoteren_US
dc.subjectDopaminergic neuronen_US
dc.subjectParkinson’s diseaseen_US
dc.subjectCell type-specific expressionen_US
dc.titleCloning and cell type-specific regulation of the human tyrosine hydroxylase gene promoteren_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.bbrc.2003.11.029-
dc.relation.journalBIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS-
dc.contributor.googleauthorKim, Tae Eun-
dc.contributor.googleauthorPark, Mi Jung-
dc.contributor.googleauthorChoi, Eun Jung-
dc.contributor.googleauthorLee, Hack Sup-
dc.contributor.googleauthorLee, Sung-Ho-
dc.contributor.googleauthorYoon, Soo Han-
dc.contributor.googleauthorOh, Chang-Kwon-
dc.contributor.googleauthorLee, Byung Ju-
dc.contributor.googleauthorKim, Seung U-
dc.contributor.googleauthorLee, Young Seek-
dc.contributor.googleauthorLee, Myung Ae-
dc.relation.code2008201235-
dc.sector.campusE-
dc.sector.daehakCOLLEGE OF SCIENCE AND CONVERGENCE TECHNOLOGY[E]-
dc.sector.departmentDEPARTMENT OF MOLECULAR AND LIFE SCIENCE-
dc.identifier.pidyslee-


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