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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1998-10-9
|
| pubmed:abstractText |
The human tryptophan hydroxylase gene (hTPH) encodes the rate-limiting enzyme in the biosynthesis of serotonin, a neurotransmitter which has been implicated in a number of psychiatric illnesses. This enzyme is expressed in a tissue-specific manner. We examined the transcriptional activity of a series of 5' deletion promoter-reporter constructs extending from nucleotide (nt) -1954 to +40 and found that the region between nt -163 and +40 contains a regulatory element important for efficient transcription of the gene, DNase I footprint analyses, using P815-HTR and HeLa nuclear protein extracts, revealed a single prominent footprint between nt -78 and -44. A cis-acting element in the footprint region was identified as an inverted CCAAT box (-67 ATTGG -63) by gel shift assays. Two base pair (bp) mutations in the core CCAAT sequence eliminated protein binding in gel shift assays and reduced transcriptional activity approximately 50% in transient transfection assays. Competitive gel shift assays showed that the protein binding to the hTPH CCAAT box was effectively competed by an oligonucleotide (oligo) harboring a binding site for CCAAT box binding factor (CBF)/nuclear factor-Y (NF-Y). A selective antibody against the B subunit of CBF/NF-Y supershifted the protein-DNA complex formed between the -90/-50 oligo probe and nuclear protein extracts. Our results indicate that the binding of CBF/NF-Y to the inverted CCAAT box is responsible for transcriptional activation of the nTPH gene.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Enhancer-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Tryptophan Hydroxylase
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Mar
|
| pubmed:issn |
0169-328X
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
30
|
| pubmed:volume |
55
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
61-70
|
| pubmed:dateRevised |
2008-11-21
|
| pubmed:meshHeading |
pubmed-meshheading:9645961-Binding Sites,
pubmed-meshheading:9645961-CCAAT-Enhancer-Binding Proteins,
pubmed-meshheading:9645961-DNA Footprinting,
pubmed-meshheading:9645961-DNA-Binding Proteins,
pubmed-meshheading:9645961-Enhancer Elements, Genetic,
pubmed-meshheading:9645961-Enzyme Induction,
pubmed-meshheading:9645961-Genes, Reporter,
pubmed-meshheading:9645961-HeLa Cells,
pubmed-meshheading:9645961-Humans,
pubmed-meshheading:9645961-Luciferases,
pubmed-meshheading:9645961-Mast-Cell Sarcoma,
pubmed-meshheading:9645961-Nerve Tissue Proteins,
pubmed-meshheading:9645961-Promoter Regions, Genetic,
pubmed-meshheading:9645961-Recombinant Fusion Proteins,
pubmed-meshheading:9645961-Serotonin,
pubmed-meshheading:9645961-Transcription, Genetic,
pubmed-meshheading:9645961-Transfection,
pubmed-meshheading:9645961-Tryptophan Hydroxylase,
pubmed-meshheading:9645961-Tumor Cells, Cultured
|
| pubmed:year |
1998
|
| pubmed:articleTitle |
CBF/NF-Y activates transcription of the human tryptophan hydroxylase gene through an inverted CCAAT box.
|
| pubmed:affiliation |
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202-5121, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|