Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dopamine beta-hydroxylase (DBH) catalyzes the conversion of dopamine to noradrenaline and is selectively expressed in noradrenergic and adrenergic neurons in the nervous system. Transient transfection assays have indicated that cell-specific transcription of the human DBH gene may require a cell-specific silencer region residing at -486 to -263 bp upstream of the transcription start site. This region includes a putative DBH negative regulatory element (DNRE) with sequence homology to the restrictive element-1 (RE1)/neuron-restrictive silencer element identified in many other neural-specific genes. However, DNRE exerted negative regulation in both neuronal and nonneuronal cells alike, and site-directed mutation of this element did not significantly diminish the repressive activity of the DBH silencer region. Furthermore, expression of RE1-silencing transcription factor/neuron-restrictive silencer factor repressed neither DBH nor tyrosine hydroxylase promoter activity. We now report identification of three protein binding sites in the silencer region of the human DBH gene: SI at -271 to -250 bp, SII at -316 to -295 bp, and SIII at -348 to -324 bp. In vitro binding studies showed that SI and SIII, but not SII, interact with nuclear proteins from DBH-negative cells in a cell-specific manner. Furthermore, SI and SIII preferentially repressed the heterologous thymidine kinase and homologous DBH proximal promoter activities in nonneuronal cells. Taken together, the cell-specific silencer function of the upstream DBH region appears to involve several cis-regulatory elements, including two cell-specific repressor elements, SI and SIII, and a general negative regulatory element, DNRE. Based on these data, we propose that a highly restricted pattern of DBH gene expression in (nor)adrenergic cells of the nervous system may be controlled by multiple negative regulatory elements/silencers.
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PMID:The cell-specific silencer region of the human dopamine beta-hydroxylase gene contains several negative regulatory elements. 964 49

Analysis of the DNA sequence of the human mu-opioid receptor gene (MOR) revealed that a region overlapping the start codon was substantially homologous to a DNA element named the neurorestrictive suppressor element (NRSE) or restrictive element 1 (RE-1). Transient transfection experiments in the L929 and HEK non-neural cell lines showed that expression of a MOR promoter/reporter gene construct was suppressed in non-neural cell lines by inclusion of this MOR NRSE. Expression from a thymidine kinase promoter was also suppressed when the MOR NRSE was inserted upstream or downstream of the reporter gene. The MOR NRSE did not suppress expression of the reporter gene in neural derived cell lines, IMR-32 and Neuro 2a. The transcription factor REST which binds NRSE thereby enacting the suppression of transcription, was encoded in a plasmid and co-transfected into the IMR-32 cells. The REST co-transfected neuronal derived (IMR-32) cells became sensitive to the MOR NRSE mediated suppression of reporter gene expression. Electrophoretic mobility shift experiments revealed that oligonucleotides containing the MOR NRSE were bound by a factor from nuclear extracts of non-neural cell lines, HeLa and Jurkat. This binding was specifically competed by oligonucleotides containing NRSE sequences previously shown to suppress transcription through REST. Thus an NRSE element overlapping the human MOR start codon suppresses gene expression in non-neural cell lines and may help direct neural tissue specific expression of MOR.
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PMID:Identification of a neurorestrictive suppressor element (NRSE) in the human mu-opioid receptor gene. 1145 94