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/S0006291X06011661https://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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