Linked Life Data

8662666

Source:http://linkedlifedata.com/resource/pubmed/id/8662666

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
1996-8-20
pubmed:abstractText
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hemopoietic growth factor that is expressed in activated T cells, fibroblasts, macrophages, and endothelial cells. Although GM-CSF does not appear to be essential for normal hemopoiesis, overexpression of GM-CSF has been implicated in the pathogenesis of some diseases such as myeloid leukemia and chronic inflammation. An NF-kappaB/Rel binding site within the GM-CSF promoter, termed the kappaB element appears to be important for controlling expression in reporter gene assays in response to a number of stimuli in T cells. We investigated oligonucleotide-directed triple helix formation across this regulatory sequence as a potential tool to inhibit GM-CSF gene transcription. A 15-base oligonucleotide, GM3, was targeted to a purine-rich region in the GM-CSF proximal promoter, which overlaps the kappaB element. Gel mobility shift assays and DNase I footprinting demonstrated that GM3 formed a sequence-specific collinear triplex with its double-stranded DNA target. Triplex formation by GM3 blocked recombinant and nuclear NF-kappaB proteins binding to the GM-CSF element. GM3 also caused selective inhibition of the human T-cell lymphotrophic virus-1 Tax transactivator-induced luciferase activity from a reporter construct driven by the GM-CSF promoter in Jurkat T cells. Finally, GM3 greatly reduced the concentration of endogenous GM-CSF mRNA induced by different stimuli in Jurkat T cells but did not affect interleukin 3 mRNA levels in the same cells. We conclude that the kappaB element in the GM-CSF promoter plays a central role in the transcriptional activation of the endogenous GM-CSF gene. Colinear triplex formation acts as a selective transcriptional repressor of the GM-CSF gene and may have potential therapeutic application in cases of undesirable overexpression of this protein.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
271
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
14438-44
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:8662666-Base Sequence, pubmed-meshheading:8662666-Binding Sites, pubmed-meshheading:8662666-Cell Line, pubmed-meshheading:8662666-DNA, pubmed-meshheading:8662666-Deoxyribonuclease I, pubmed-meshheading:8662666-Gene Products, tax, pubmed-meshheading:8662666-Granulocyte-Macrophage Colony-Stimulating Factor, pubmed-meshheading:8662666-Human T-lymphotropic virus 1, pubmed-meshheading:8662666-Humans, pubmed-meshheading:8662666-Leukemia, Myeloid, pubmed-meshheading:8662666-Luciferases, pubmed-meshheading:8662666-Molecular Sequence Data, pubmed-meshheading:8662666-NF-kappa B, pubmed-meshheading:8662666-Nucleic Acid Conformation, pubmed-meshheading:8662666-Oligodeoxyribonucleotides, pubmed-meshheading:8662666-Promoter Regions, Genetic, pubmed-meshheading:8662666-T-Lymphocytes, pubmed-meshheading:8662666-Tetradecanoylphorbol Acetate, pubmed-meshheading:8662666-Transcription, Genetic, pubmed-meshheading:8662666-Tumor Cells, Cultured
pubmed:year
1996
pubmed:articleTitle
DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.
pubmed:affiliation
Division of Human Immunology, Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Frome Road, Adelaide 5000, South Australia, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't