Id |
Subject |
Object |
Predicate |
Lexical cue |
S1 |
0-125 |
Sentence |
denotes |
DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells. |
S2 |
126-303 |
Sentence |
denotes |
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hemopoietic growth factor that is expressed in activated T cells, fibroblasts, macrophages, and endothelial cells. |
S3 |
304-508 |
Sentence |
denotes |
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. |
S4 |
509-714 |
Sentence |
denotes |
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. |
S5 |
715-868 |
Sentence |
denotes |
We investigated oligonucleotide-directed triple helix formation across this regulatory sequence as a potential tool to inhibit GM-CSF gene transcription. |
S6 |
869-1005 |
Sentence |
denotes |
A 15-base oligonucleotide, GM3, was targeted to a purine-rich region in the GM-CSF proximal promoter, which overlaps the kappaB element. |
S7 |
1006-1160 |
Sentence |
denotes |
Gel mobility shift assays and DNase I footprinting demonstrated that GM3 formed a sequence-specific collinear triplex with its double-stranded DNA target. |
S8 |
1161-1267 |
Sentence |
denotes |
Triplex formation by GM3 blocked recombinant and nuclear NF-kappaB proteins binding to the GM-CSF element. |
S9 |
1268-1468 |
Sentence |
denotes |
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. |
S10 |
1469-1652 |
Sentence |
denotes |
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. |
S11 |
1653-1797 |
Sentence |
denotes |
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. |
S12 |
1798-1992 |
Sentence |
denotes |
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. |