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Regulation of human tyrosine hydroxylase gene by neuron-restrictive silencer factor

Title
Regulation of human tyrosine hydroxylase gene by neuron-restrictive silencer factor
Author
이영식
Keywords
tyrosine hydroxylase; promoter; repression; NRSF/REST; NRSE/RE1; catecholaminergic; neural stem cells
Issue Date
2006-06
Publisher
ACADEMIC PRESS INC
Citation
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v. 346, No. 2, Page. 426-435
Abstract
Tyrosine hydroxylase (TH), the biosynthetic enzyme of catecholamine, is synthesized specifically in catecholaminergic neurons. Thus, it is possible that neuronal cell type-specific expression of this gene is coordinately regulated. One of the neuron- specific transcription regulators, neuron-restrictive silencer factor (NRSF)/ repressor element 1 (RE1) silencing transcription factor (REST), represses the expression of neuronal genes in non-neuronal cells. To elucidate the molecular mechanisms that control catecholaminergic neuronal expression of human TH, we initially characterized the 50 regulatory region. Previous studies have shown that a 3174 bp fragment of the human TH promoter confers specific expression to the reporter gene in dopaminergic neuron-like cell lines. Within this 50 regulatory region, three putative neuron-restrictive silencer elements (NRSE)/RE1 were identified, which bound NRSF/REST in a sequence-specific manner, as confirmed using EMSA and ChIP assays. In transient transfection assays, deletion or mutation of NRSE/RE1 elements led to a 7-fold increase in activity of the 3.2 kb TH promoter in human neural stem cells (NSCs), but had no major effects on differentiated neuron- like cells. Suppression of NRSF/REST functions with either the histone deacetylase inhibitor, trichostatin, or DN-NRSFinduced TH promoter activity. Our data strongly suggest that NRSF/REST functions as a repressor of TH transcription in NSCs via a mechanism dependent on the TH NRSE/RE1 sites.
URI
https://www.sciencedirect.com/science/article/pii/S0006291X06011661http://repository.hanyang.ac.kr/handle/20.500.11754/108216
ISSN
0006-291X; 1090-2104
DOI
10.1016/j.bbrc.2006.05.142
Appears in Collections:
COLLEGE OF SCIENCE AND CONVERGENCE TECHNOLOGY[E](과학기술융합대학) > MOLECULAR AND LIFE SCIENCE(분자생명과학과) > Articles
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