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)

Synapsin Ia and synapsin Ib are abundant synaptic vesicle proteins that are derived by differential splicing from a single gene. To identify control elements directing the neuronal expression of synapsins Ia/b, we functionally analyzed the promoter region of the human synapsin I gene. A hybrid gene was constructed containing 2 kilobases of 5' flanking sequence from the synapsin I gene fused to the bacterial gene chloramphenicol acetyltransferase and transfected into 12 different neuronal and nonneuronal cell lines. In general, expression of the chimeric reporter gene showed excellent correlation with endogenous expression of synapsin I in different neuronal cell lines, whereas transcription was low in all nonneuronal cell lines examined. The addition of the simian virus 40 enhancer promoted non-tissue-specific expression. Deletion mutagenesis of the synapsin I promoter revealed the presence of positive and negative sequence elements. A basal (constitutive) promoter that directs reporter gene expression in neuronal and nonneuronal cell lines was mapped to the region -115 to +47. The promoter region from -422 to -22 contains positive elements that upon fusion with the herpes simplex virus thymidine kinase promoter potentiate its transcription in PC12 and neuroblastoma cells but not in Chinese hamster ovary cells.
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PMID:Characterization of tissue-specific transcription by the human synapsin I gene promoter. 184 57

Transient transfection experiments indicate that a 5'-flanking upstream domain, residing between -437 and -262 bp of the human dopamine beta-hydroxylase (DBH) gene, has a cell type-specific silencer function. This domain contains a putative silencer motif (which we designate DBH negative regulatory element, DNRE), showing sequence homology with the neural-restrictive silencer element (NRSE or RE-1) recently characterized in type II sodium channel, SCG10 and synapsin I genes. When the DNRE was placed at the proximal 262 bp of the homologous (DBH) promoter, it exhibited strong silencer activity both in DBH-expressing SK-N-BE(2)C as well as in DBH-nonexpressing HeLa cells. In addition, the DNRE also exhibited modest silencer activity upon a heterologous tk (herpes simplex virus thymidine kinase) promoter in both cell lines. Electrophoretic mobility shift assay demonstrated that nuclear extracts from both SK-N-BE(2)C and HeLa cells contain protein(s) that specifically bind to the DNRE. Formation of this DNRE/protein complex was specifically inhibited by an excess of unlabeled DNRE or NRSE. Finally, a similar sequence motif residing in the corresponding upstream area of the rat DBH gene also had a negative regulatory function, indicating that the silencer function of the DNRE is conserved in human and rat DBH genes.
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PMID:Identification of a negative regulatory element in the 5'-flanking region of the human dopamine beta-hydroxylase gene. 875 Aug 28