PubMed:8662666 JSONTXT

{"project":"Test-Species-PubTator","denotations":[{"id":"2","span":{"begin":43,"end":91},"obj":"Gene"},{"id":"3","span":{"begin":111,"end":116},"obj":"Species"},{"id":"30","span":{"begin":126,"end":174},"obj":"Gene"},{"id":"31","span":{"begin":176,"end":182},"obj":"Gene"},{"id":"32","span":{"begin":313,"end":319},"obj":"Gene"},{"id":"33","span":{"begin":394,"end":400},"obj":"Gene"},{"id":"34","span":{"begin":466,"end":482},"obj":"Disease"},{"id":"35","span":{"begin":487,"end":507},"obj":"Disease"},{"id":"36","span":{"begin":512,"end":521},"obj":"Gene"},{"id":"37","span":{"begin":550,"end":556},"obj":"Gene"},{"id":"38","span":{"begin":731,"end":746},"obj":"Chemical"},{"id":"39","span":{"begin":842,"end":848},"obj":"Gene"},{"id":"40","span":{"begin":879,"end":894},"obj":"Chemical"},{"id":"41","span":{"begin":945,"end":951},"obj":"Gene"},{"id":"42","span":{"begin":1218,"end":1227},"obj":"Gene"},{"id":"43","span":{"begin":1252,"end":1258},"obj":"Gene"},{"id":"44","span":{"begin":1268,"end":1271},"obj":"Chemical"},{"id":"45","span":{"begin":1312,"end":1317},"obj":"Species"},{"id":"46","span":{"begin":1318,"end":1346},"obj":"Species"},{"id":"47","span":{"begin":1434,"end":1440},"obj":"Gene"},{"id":"48","span":{"begin":1453,"end":1461},"obj":"CellLine"},{"id":"49","span":{"begin":1478,"end":1481},"obj":"Chemical"},{"id":"50","span":{"begin":1530,"end":1536},"obj":"Gene"},{"id":"51","span":{"begin":1574,"end":1582},"obj":"CellLine"},{"id":"52","span":{"begin":1608,"end":1621},"obj":"Gene"},{"id":"53","span":{"begin":1696,"end":1702},"obj":"Gene"},{"id":"54","span":{"begin":1785,"end":1791},"obj":"Gene"},{"id":"55","span":{"begin":1878,"end":1884},"obj":"Gene"}],"attributes":[{"id":"A2","pred":"resolved_to","subj":"2","obj":"1437"},{"id":"A3","pred":"resolved_to","subj":"3","obj":"9606"},{"id":"A30","pred":"resolved_to","subj":"30","obj":"1437"},{"id":"A31","pred":"resolved_to","subj":"31","obj":"1437"},{"id":"A32","pred":"resolved_to","subj":"32","obj":"1437"},{"id":"A33","pred":"resolved_to","subj":"33","obj":"1437"},{"id":"A34","pred":"resolved_to","subj":"34","obj":"MESH:D007951"},{"id":"A35","pred":"resolved_to","subj":"35","obj":"MESH:D007249"},{"id":"A36","pred":"resolved_to","subj":"36","obj":"4790"},{"id":"A37","pred":"resolved_to","subj":"37","obj":"1437"},{"id":"A38","pred":"resolved_to","subj":"38","obj":"MESH:D009841"},{"id":"A39","pred":"resolved_to","subj":"39","obj":"1437"},{"id":"A40","pred":"resolved_to","subj":"40","obj":"MESH:D009841"},{"id":"A41","pred":"resolved_to","subj":"41","obj":"1437"},{"id":"A42","pred":"resolved_to","subj":"42","obj":"4790"},{"id":"A43","pred":"resolved_to","subj":"43","obj":"1437"},{"id":"A44","pred":"resolved_to","subj":"44","obj":"-"},{"id":"A45","pred":"resolved_to","subj":"45","obj":"9606"},{"id":"A47","pred":"resolved_to","subj":"47","obj":"1437"},{"id":"A48","pred":"resolved_to","subj":"48","obj":"CVCL:0065"},{"id":"A49","pred":"resolved_to","subj":"49","obj":"-"},{"id":"A50","pred":"resolved_to","subj":"50","obj":"1437"},{"id":"A51","pred":"resolved_to","subj":"51","obj":"CVCL:0065"},{"id":"A52","pred":"resolved_to","subj":"52","obj":"3562"},{"id":"A53","pred":"resolved_to","subj":"53","obj":"1437"},{"id":"A54","pred":"resolved_to","subj":"54","obj":"1437"},{"id":"A55","pred":"resolved_to","subj":"55","obj":"1437"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"Test-Species-PubDictionaries","denotations":[{"id":"T1","span":{"begin":111,"end":116},"obj":"OrganismTaxon"},{"id":"T2","span":{"begin":1312,"end":1317},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"9606"},{"id":"A2","pred":"db_id","subj":"T2","obj":"9606"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"Test-Species-PubDictionaries-PubMedBERT","denotations":[{"id":"T1","span":{"begin":4,"end":11},"obj":"Species"},{"id":"T2","span":{"begin":111,"end":116},"obj":"Species"},{"id":"T3","span":{"begin":356,"end":362},"obj":"Species"},{"id":"T4","span":{"begin":756,"end":762},"obj":"Species"},{"id":"T5","span":{"begin":763,"end":768},"obj":"Species"},{"id":"T6","span":{"begin":1116,"end":1123},"obj":"Species"},{"id":"T7","span":{"begin":1161,"end":1168},"obj":"Species"},{"id":"T8","span":{"begin":1272,"end":1276},"obj":"Species"},{"id":"T9","span":{"begin":1312,"end":1317},"obj":"Species"},{"id":"T10","span":{"begin":1318,"end":1346},"obj":"Species"},{"id":"T11","span":{"begin":1347,"end":1350},"obj":"Species"},{"id":"T12","span":{"begin":1641,"end":1645},"obj":"Species"},{"id":"T13","span":{"begin":1807,"end":1814},"obj":"Species"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"451987"},{"id":"A2","pred":"db_id","subj":"T2","obj":"9606"},{"id":"A3","pred":"db_id","subj":"T3","obj":"2974449"},{"id":"A4","pred":"db_id","subj":"T4","obj":"451987"},{"id":"A5","pred":"db_id","subj":"T5","obj":"1407192"},{"id":"A6","pred":"db_id","subj":"T6","obj":"451987"},{"id":"A7","pred":"db_id","subj":"T7","obj":"451987"},{"id":"A8","pred":"db_id","subj":"T8","obj":"209674"},{"id":"A9","pred":"db_id","subj":"T9","obj":"9606"},{"id":"A10","pred":"db_id","subj":"T10","obj":"194440"},{"id":"A11","pred":"db_id","subj":"T11","obj":"1369706"},{"id":"A12","pred":"db_id","subj":"T12","obj":"582003"},{"id":"A13","pred":"db_id","subj":"T13","obj":"451987"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"GlyCosmos6-Glycan-Motif-Image","denotations":[{"id":"T1","span":{"begin":896,"end":899},"obj":"Glycan_Motif"},{"id":"T3","span":{"begin":1075,"end":1078},"obj":"Glycan_Motif"},{"id":"T5","span":{"begin":1182,"end":1185},"obj":"Glycan_Motif"},{"id":"T7","span":{"begin":1268,"end":1271},"obj":"Glycan_Motif"},{"id":"T9","span":{"begin":1478,"end":1481},"obj":"Glycan_Motif"}],"attributes":[{"id":"A1","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G91237TK"},{"id":"A2","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G56516VH"},{"id":"A3","pred":"image","subj":"T3","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G91237TK"},{"id":"A4","pred":"image","subj":"T3","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G56516VH"},{"id":"A5","pred":"image","subj":"T5","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G91237TK"},{"id":"A6","pred":"image","subj":"T5","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G56516VH"},{"id":"A7","pred":"image","subj":"T7","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G91237TK"},{"id":"A8","pred":"image","subj":"T7","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G56516VH"},{"id":"A9","pred":"image","subj":"T9","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G91237TK"},{"id":"A10","pred":"image","subj":"T9","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G56516VH"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"sentences","denotations":[{"id":"T1","span":{"begin":0,"end":125},"obj":"Sentence"},{"id":"T2","span":{"begin":126,"end":303},"obj":"Sentence"},{"id":"T3","span":{"begin":304,"end":508},"obj":"Sentence"},{"id":"T4","span":{"begin":509,"end":714},"obj":"Sentence"},{"id":"T5","span":{"begin":715,"end":868},"obj":"Sentence"},{"id":"T6","span":{"begin":869,"end":1005},"obj":"Sentence"},{"id":"T7","span":{"begin":1006,"end":1160},"obj":"Sentence"},{"id":"T8","span":{"begin":1161,"end":1267},"obj":"Sentence"},{"id":"T9","span":{"begin":1268,"end":1468},"obj":"Sentence"},{"id":"T10","span":{"begin":1469,"end":1652},"obj":"Sentence"},{"id":"T11","span":{"begin":1653,"end":1797},"obj":"Sentence"},{"id":"T12","span":{"begin":1798,"end":1992},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":125},"obj":"Sentence"},{"id":"T2","span":{"begin":126,"end":303},"obj":"Sentence"},{"id":"T3","span":{"begin":304,"end":508},"obj":"Sentence"},{"id":"T4","span":{"begin":509,"end":714},"obj":"Sentence"},{"id":"T5","span":{"begin":715,"end":868},"obj":"Sentence"},{"id":"T6","span":{"begin":869,"end":1005},"obj":"Sentence"},{"id":"T7","span":{"begin":1006,"end":1160},"obj":"Sentence"},{"id":"T8","span":{"begin":1161,"end":1267},"obj":"Sentence"},{"id":"T9","span":{"begin":1268,"end":1468},"obj":"Sentence"},{"id":"T10","span":{"begin":1469,"end":1652},"obj":"Sentence"},{"id":"T11","span":{"begin":1653,"end":1797},"obj":"Sentence"},{"id":"T12","span":{"begin":1798,"end":1992},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"GlyCosmos6-Glycan-Motif-Structure","denotations":[{"id":"T1","span":{"begin":896,"end":899},"obj":"https://glytoucan.org/Structures/Glycans/G56516VH"},{"id":"T2","span":{"begin":896,"end":899},"obj":"https://glytoucan.org/Structures/Glycans/G91237TK"},{"id":"T3","span":{"begin":1075,"end":1078},"obj":"https://glytoucan.org/Structures/Glycans/G56516VH"},{"id":"T4","span":{"begin":1075,"end":1078},"obj":"https://glytoucan.org/Structures/Glycans/G91237TK"},{"id":"T5","span":{"begin":1182,"end":1185},"obj":"https://glytoucan.org/Structures/Glycans/G56516VH"},{"id":"T6","span":{"begin":1182,"end":1185},"obj":"https://glytoucan.org/Structures/Glycans/G91237TK"},{"id":"T7","span":{"begin":1268,"end":1271},"obj":"https://glytoucan.org/Structures/Glycans/G56516VH"},{"id":"T8","span":{"begin":1268,"end":1271},"obj":"https://glytoucan.org/Structures/Glycans/G91237TK"},{"id":"T9","span":{"begin":1478,"end":1481},"obj":"https://glytoucan.org/Structures/Glycans/G56516VH"},{"id":"T10","span":{"begin":1478,"end":1481},"obj":"https://glytoucan.org/Structures/Glycans/G91237TK"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"Glycosmos6-MAT","denotations":[{"id":"T1","span":{"begin":952,"end":960},"obj":"http://purl.obolibrary.org/obo/MAT_0000491"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"Inflammaging","denotations":[{"id":"T1","span":{"begin":0,"end":125},"obj":"Sentence"},{"id":"T2","span":{"begin":126,"end":303},"obj":"Sentence"},{"id":"T3","span":{"begin":304,"end":508},"obj":"Sentence"},{"id":"T4","span":{"begin":509,"end":714},"obj":"Sentence"},{"id":"T5","span":{"begin":715,"end":868},"obj":"Sentence"},{"id":"T6","span":{"begin":869,"end":1005},"obj":"Sentence"},{"id":"T7","span":{"begin":1006,"end":1160},"obj":"Sentence"},{"id":"T8","span":{"begin":1161,"end":1267},"obj":"Sentence"},{"id":"T9","span":{"begin":1268,"end":1468},"obj":"Sentence"},{"id":"T10","span":{"begin":1469,"end":1652},"obj":"Sentence"},{"id":"T11","span":{"begin":1653,"end":1797},"obj":"Sentence"},{"id":"T12","span":{"begin":1798,"end":1992},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":125},"obj":"Sentence"},{"id":"T2","span":{"begin":126,"end":303},"obj":"Sentence"},{"id":"T3","span":{"begin":304,"end":508},"obj":"Sentence"},{"id":"T4","span":{"begin":509,"end":714},"obj":"Sentence"},{"id":"T5","span":{"begin":715,"end":868},"obj":"Sentence"},{"id":"T6","span":{"begin":869,"end":1005},"obj":"Sentence"},{"id":"T7","span":{"begin":1006,"end":1160},"obj":"Sentence"},{"id":"T8","span":{"begin":1161,"end":1267},"obj":"Sentence"},{"id":"T9","span":{"begin":1268,"end":1468},"obj":"Sentence"},{"id":"T10","span":{"begin":1469,"end":1652},"obj":"Sentence"},{"id":"T11","span":{"begin":1653,"end":1797},"obj":"Sentence"},{"id":"T12","span":{"begin":1798,"end":1992},"obj":"Sentence"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":313,"end":319},"obj":"gene:1437"},{"id":"T1","span":{"begin":466,"end":482},"obj":"disease:C0023470"},{"id":"T2","span":{"begin":394,"end":400},"obj":"gene:1437"},{"id":"T3","span":{"begin":466,"end":482},"obj":"disease:C0023470"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"jnlpba-st-training","denotations":[{"id":"T1","span":{"begin":43,"end":96},"obj":"DNA"},{"id":"T2","span":{"begin":126,"end":174},"obj":"protein"},{"id":"T3","span":{"begin":176,"end":182},"obj":"protein"},{"id":"T4","span":{"begin":313,"end":319},"obj":"protein"},{"id":"T5","span":{"begin":512,"end":521},"obj":"protein"},{"id":"T6","span":{"begin":550,"end":565},"obj":"DNA"},{"id":"T7","span":{"begin":647,"end":660},"obj":"DNA"},{"id":"T8","span":{"begin":706,"end":713},"obj":"cell_type"},{"id":"T9","span":{"begin":791,"end":810},"obj":"DNA"},{"id":"T10","span":{"begin":842,"end":848},"obj":"protein"},{"id":"T11","span":{"begin":919,"end":937},"obj":"DNA"},{"id":"T12","span":{"begin":945,"end":969},"obj":"DNA"},{"id":"T13","span":{"begin":990,"end":1004},"obj":"DNA"},{"id":"T14","span":{"begin":1036,"end":1043},"obj":"protein"},{"id":"T15","span":{"begin":1133,"end":1159},"obj":"DNA"},{"id":"T16","span":{"begin":1194,"end":1236},"obj":"protein"},{"id":"T17","span":{"begin":1252,"end":1266},"obj":"DNA"},{"id":"T18","span":{"begin":1312,"end":1350},"obj":"protein"},{"id":"T19","span":{"begin":1374,"end":1384},"obj":"protein"},{"id":"T20","span":{"begin":1434,"end":1449},"obj":"DNA"},{"id":"T21","span":{"begin":1453,"end":1467},"obj":"cell_line"},{"id":"T22","span":{"begin":1530,"end":1541},"obj":"RNA"},{"id":"T23","span":{"begin":1574,"end":1588},"obj":"cell_line"},{"id":"T24","span":{"begin":1608,"end":1626},"obj":"RNA"},{"id":"T25","span":{"begin":1674,"end":1688},"obj":"DNA"},{"id":"T26","span":{"begin":1696,"end":1711},"obj":"DNA"},{"id":"T27","span":{"begin":1785,"end":1796},"obj":"DNA"},{"id":"T28","span":{"begin":1878,"end":1889},"obj":"DNA"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"DisGeNET5_gene_disease","denotations":[{"id":"8662666-2#9#15#gene1437","span":{"begin":313,"end":319},"obj":"gene1437"},{"id":"8662666-2#90#96#gene1437","span":{"begin":394,"end":400},"obj":"gene1437"},{"id":"8662666-2#162#178#diseaseC0023470","span":{"begin":466,"end":482},"obj":"diseaseC0023470"}],"relations":[{"id":"9#15#gene1437162#178#diseaseC0023470","pred":"associated_with","subj":"8662666-2#9#15#gene1437","obj":"8662666-2#162#178#diseaseC0023470"},{"id":"90#96#gene1437162#178#diseaseC0023470","pred":"associated_with","subj":"8662666-2#90#96#gene1437","obj":"8662666-2#162#178#diseaseC0023470"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"GENIAcorpus","denotations":[{"id":"T1","span":{"begin":0,"end":21},"obj":"other_name"},{"id":"T2","span":{"begin":43,"end":91},"obj":"protein_molecule"},{"id":"T3","span":{"begin":126,"end":174},"obj":"protein_molecule"},{"id":"T4","span":{"begin":176,"end":182},"obj":"protein_molecule"},{"id":"T5","span":{"begin":313,"end":319},"obj":"protein_molecule"},{"id":"T6","span":{"begin":512,"end":521},"obj":"protein_complex"},{"id":"T7","span":{"begin":550,"end":556},"obj":"protein_molecule"},{"id":"T8","span":{"begin":647,"end":660},"obj":"DNA_family_or_group"},{"id":"T9","span":{"begin":706,"end":713},"obj":"cell_type"},{"id":"T10","span":{"begin":731,"end":746},"obj":"polynucleotide"},{"id":"T11","span":{"begin":791,"end":810},"obj":"DNA_domain_or_region"},{"id":"T12","span":{"begin":842,"end":848},"obj":"protein_molecule"},{"id":"T13","span":{"begin":871,"end":894},"obj":"polynucleotide"},{"id":"T14","span":{"begin":896,"end":899},"obj":"polynucleotide"},{"id":"T15","span":{"begin":919,"end":937},"obj":"DNA_domain_or_region"},{"id":"T16","span":{"begin":945,"end":951},"obj":"protein_molecule"},{"id":"T17","span":{"begin":990,"end":1004},"obj":"DNA_domain_or_region"},{"id":"T18","span":{"begin":1006,"end":1031},"obj":"other_name"},{"id":"T19","span":{"begin":1036,"end":1043},"obj":"protein_molecule"},{"id":"T20","span":{"begin":1075,"end":1078},"obj":"polynucleotide"},{"id":"T21","span":{"begin":1088,"end":1123},"obj":"DNA_substructure"},{"id":"T22","span":{"begin":1133,"end":1159},"obj":"DNA_domain_or_region"},{"id":"T23","span":{"begin":1161,"end":1178},"obj":"other_name"},{"id":"T24","span":{"begin":1182,"end":1185},"obj":"polynucleotide"},{"id":"T25","span":{"begin":1252,"end":1258},"obj":"protein_molecule"},{"id":"T26","span":{"begin":1268,"end":1271},"obj":"polynucleotide"},{"id":"T27","span":{"begin":1312,"end":1346},"obj":"virus"},{"id":"T28","span":{"begin":1374,"end":1384},"obj":"protein_molecule"},{"id":"T29","span":{"begin":1434,"end":1440},"obj":"protein_molecule"},{"id":"T30","span":{"begin":1453,"end":1467},"obj":"cell_line"},{"id":"T31","span":{"begin":1478,"end":1481},"obj":"polynucleotide"},{"id":"T32","span":{"begin":1530,"end":1536},"obj":"protein_molecule"},{"id":"T33","span":{"begin":1574,"end":1588},"obj":"cell_line"},{"id":"T34","span":{"begin":1608,"end":1621},"obj":"protein_molecule"},{"id":"T35","span":{"begin":1674,"end":1688},"obj":"DNA_domain_or_region"},{"id":"T36","span":{"begin":1696,"end":1702},"obj":"protein_molecule"},{"id":"T37","span":{"begin":1740,"end":1766},"obj":"other_name"},{"id":"T38","span":{"begin":1785,"end":1791},"obj":"protein_molecule"},{"id":"T39","span":{"begin":1798,"end":1824},"obj":"other_name"},{"id":"T40","span":{"begin":1845,"end":1870},"obj":"other_name"},{"id":"T41","span":{"begin":1878,"end":1884},"obj":"protein_molecule"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"pubmed-sentences-benchmark","denotations":[{"id":"S1","span":{"begin":0,"end":125},"obj":"Sentence"},{"id":"S2","span":{"begin":126,"end":303},"obj":"Sentence"},{"id":"S3","span":{"begin":304,"end":508},"obj":"Sentence"},{"id":"S4","span":{"begin":509,"end":714},"obj":"Sentence"},{"id":"S5","span":{"begin":715,"end":868},"obj":"Sentence"},{"id":"S6","span":{"begin":869,"end":1005},"obj":"Sentence"},{"id":"S7","span":{"begin":1006,"end":1160},"obj":"Sentence"},{"id":"S8","span":{"begin":1161,"end":1267},"obj":"Sentence"},{"id":"S9","span":{"begin":1268,"end":1468},"obj":"Sentence"},{"id":"S10","span":{"begin":1469,"end":1652},"obj":"Sentence"},{"id":"S11","span":{"begin":1653,"end":1797},"obj":"Sentence"},{"id":"S12","span":{"begin":1798,"end":1992},"obj":"Sentence"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"genia-medco-coref","denotations":[{"id":"C7","span":{"begin":111,"end":124},"obj":"NP"},{"id":"C1","span":{"begin":126,"end":183},"obj":"NP"},{"id":"C2","span":{"begin":187,"end":214},"obj":"NP"},{"id":"C3","span":{"begin":215,"end":219},"obj":"NP"},{"id":"C4","span":{"begin":313,"end":319},"obj":"NP"},{"id":"C5","span":{"begin":394,"end":400},"obj":"NP"},{"id":"C6","span":{"begin":546,"end":565},"obj":"NP"},{"id":"C13","span":{"begin":574,"end":592},"obj":"NP"},{"id":"C8","span":{"begin":706,"end":713},"obj":"NP"},{"id":"C9","span":{"begin":869,"end":894},"obj":"NP"},{"id":"C10","span":{"begin":896,"end":899},"obj":"NP"},{"id":"C11","span":{"begin":941,"end":969},"obj":"NP"},{"id":"C12","span":{"begin":971,"end":976},"obj":"NP"},{"id":"C14","span":{"begin":986,"end":1004},"obj":"NP"},{"id":"C15","span":{"begin":1075,"end":1078},"obj":"NP"},{"id":"C16","span":{"begin":1129,"end":1132},"obj":"NP"},{"id":"C17","span":{"begin":1182,"end":1185},"obj":"NP"},{"id":"C18","span":{"begin":1248,"end":1266},"obj":"NP"},{"id":"C19","span":{"begin":1268,"end":1271},"obj":"NP"},{"id":"C20","span":{"begin":1430,"end":1449},"obj":"NP"},{"id":"C22","span":{"begin":1453,"end":1467},"obj":"NP"},{"id":"C21","span":{"begin":1478,"end":1481},"obj":"NP"},{"id":"C23","span":{"begin":1574,"end":1588},"obj":"NP"},{"id":"C24","span":{"begin":1637,"end":1651},"obj":"NP"},{"id":"C25","span":{"begin":1692,"end":1711},"obj":"NP"},{"id":"C26","span":{"begin":1670,"end":1711},"obj":"NP"},{"id":"C27","span":{"begin":1979,"end":1991},"obj":"NP"}],"relations":[{"id":"R1","pred":"coref-relat","subj":"C3","obj":"C2"},{"id":"R2","pred":"coref-ident","subj":"C4","obj":"C1"},{"id":"R3","pred":"coref-ident","subj":"C5","obj":"C4"},{"id":"R4","pred":"coref-ident","subj":"C13","obj":"C6"},{"id":"R5","pred":"coref-ident","subj":"C8","obj":"C7"},{"id":"R6","pred":"coref-appos","subj":"C10","obj":"C9"},{"id":"R7","pred":"coref-other","subj":"C11","obj":"C6"},{"id":"R8","pred":"coref-relat","subj":"C12","obj":"C11"},{"id":"R9","pred":"coref-ident","subj":"C14","obj":"C13"},{"id":"R10","pred":"coref-ident","subj":"C15","obj":"C10"},{"id":"R11","pred":"coref-pron","subj":"C16","obj":"C15"},{"id":"R12","pred":"coref-ident","subj":"C17","obj":"C15"},{"id":"R13","pred":"coref-ident","subj":"C18","obj":"C11"},{"id":"R14","pred":"coref-ident","subj":"C19","obj":"C17"},{"id":"R15","pred":"coref-ident","subj":"C20","obj":"C6"},{"id":"R16","pred":"coref-ident","subj":"C21","obj":"C19"},{"id":"R17","pred":"coref-ident","subj":"C23","obj":"C22"},{"id":"R18","pred":"coref-ident","subj":"C24","obj":"C23"},{"id":"R19","pred":"coref-ident","subj":"C25","obj":"C20"},{"id":"R20","pred":"coref-ident","subj":"C26","obj":"C13"},{"id":"R21","pred":"coref-ident","subj":"C27","obj":"C5"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"GlyCosmos15-Glycan","denotations":[{"id":"T1","span":{"begin":896,"end":899},"obj":"Glycan"},{"id":"T2","span":{"begin":1075,"end":1078},"obj":"Glycan"},{"id":"T3","span":{"begin":1182,"end":1185},"obj":"Glycan"},{"id":"T4","span":{"begin":1268,"end":1271},"obj":"Glycan"},{"id":"T5","span":{"begin":1478,"end":1481},"obj":"Glycan"}],"attributes":[{"id":"A1","pred":"glycosmos_id","subj":"T1","obj":"https://glycosmos.org/glycans/show/G91237TK"},{"id":"A6","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G91237TK"},{"id":"A2","pred":"glycosmos_id","subj":"T2","obj":"https://glycosmos.org/glycans/show/G91237TK"},{"id":"A7","pred":"image","subj":"T2","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G91237TK"},{"id":"A3","pred":"glycosmos_id","subj":"T3","obj":"https://glycosmos.org/glycans/show/G91237TK"},{"id":"A8","pred":"image","subj":"T3","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G91237TK"},{"id":"A4","pred":"glycosmos_id","subj":"T4","obj":"https://glycosmos.org/glycans/show/G91237TK"},{"id":"A9","pred":"image","subj":"T4","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G91237TK"},{"id":"A5","pred":"glycosmos_id","subj":"T5","obj":"https://glycosmos.org/glycans/show/G91237TK"},{"id":"A10","pred":"image","subj":"T5","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G91237TK"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"Anatomy-MAT","denotations":[{"id":"T1","span":{"begin":952,"end":960},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"mat_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MAT_0000491"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"HP-phenotype","denotations":[{"id":"T1","span":{"begin":466,"end":482},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"HP:0012324"}],"namespaces":[{"prefix":"HP","uri":"http://purl.obolibrary.org/obo/HP_"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":466,"end":494},"obj":"Disease"},{"id":"T2","span":{"begin":495,"end":507},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0011996"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0021166"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"Glycan-GlyCosmos","denotations":[{"id":"T1","span":{"begin":896,"end":899},"obj":"Glycan"},{"id":"T2","span":{"begin":1075,"end":1078},"obj":"Glycan"},{"id":"T3","span":{"begin":1182,"end":1185},"obj":"Glycan"},{"id":"T4","span":{"begin":1268,"end":1271},"obj":"Glycan"},{"id":"T5","span":{"begin":1478,"end":1481},"obj":"Glycan"}],"attributes":[{"id":"A1","pred":"glycosmos_id","subj":"T1","obj":"https://glycosmos.org/glycans/show/G91237TK"},{"id":"A6","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G91237TK"},{"id":"A2","pred":"glycosmos_id","subj":"T2","obj":"https://glycosmos.org/glycans/show/G91237TK"},{"id":"A7","pred":"image","subj":"T2","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G91237TK"},{"id":"A3","pred":"glycosmos_id","subj":"T3","obj":"https://glycosmos.org/glycans/show/G91237TK"},{"id":"A8","pred":"image","subj":"T3","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G91237TK"},{"id":"A4","pred":"glycosmos_id","subj":"T4","obj":"https://glycosmos.org/glycans/show/G91237TK"},{"id":"A9","pred":"image","subj":"T4","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G91237TK"},{"id":"A5","pred":"glycosmos_id","subj":"T5","obj":"https://glycosmos.org/glycans/show/G91237TK"},{"id":"A10","pred":"image","subj":"T5","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G91237TK"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"GlyCosmos15-HP","denotations":[{"id":"T1","span":{"begin":466,"end":482},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"HP:0012324"}],"namespaces":[{"prefix":"HP","uri":"http://purl.obolibrary.org/obo/HP_"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"Organism-PubDic","denotations":[{"id":"T1","span":{"begin":111,"end":116},"obj":"Species"},{"id":"T2","span":{"begin":1312,"end":1317},"obj":"Species"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"9606"},{"id":"A2","pred":"db_id","subj":"T2","obj":"9606"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"Organism-PubTator","denotations":[{"id":"3","span":{"begin":111,"end":116},"obj":"Species"},{"id":"45","span":{"begin":1312,"end":1317},"obj":"Species"},{"id":"46","span":{"begin":1318,"end":1346},"obj":"Species"}],"attributes":[{"id":"A3","pred":"db_id","subj":"3","obj":"9606"},{"id":"A45","pred":"db_id","subj":"45","obj":"9606"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"Organism-PubDic-Bert-9","denotations":[{"id":"T1","span":{"begin":111,"end":116},"obj":"Species"},{"id":"T2","span":{"begin":1312,"end":1317},"obj":"Species"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"9606"},{"id":"A2","pred":"db_id","subj":"T2","obj":"9606"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"Organism-PubDic-Bert-8","denotations":[{"id":"T1","span":{"begin":4,"end":11},"obj":"Species"},{"id":"T2","span":{"begin":111,"end":116},"obj":"Species"},{"id":"T3","span":{"begin":356,"end":362},"obj":"Species"},{"id":"T4","span":{"begin":756,"end":762},"obj":"Species"},{"id":"T5","span":{"begin":763,"end":768},"obj":"Species"},{"id":"T6","span":{"begin":1116,"end":1123},"obj":"Species"},{"id":"T7","span":{"begin":1161,"end":1168},"obj":"Species"},{"id":"T8","span":{"begin":1272,"end":1276},"obj":"Species"},{"id":"T9","span":{"begin":1312,"end":1317},"obj":"Species"},{"id":"T10","span":{"begin":1318,"end":1346},"obj":"Species"},{"id":"T11","span":{"begin":1347,"end":1350},"obj":"Species"},{"id":"T12","span":{"begin":1641,"end":1645},"obj":"Species"},{"id":"T13","span":{"begin":1807,"end":1814},"obj":"Species"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"451987"},{"id":"A2","pred":"db_id","subj":"T2","obj":"9606"},{"id":"A3","pred":"db_id","subj":"T3","obj":"2974449"},{"id":"A4","pred":"db_id","subj":"T4","obj":"451987"},{"id":"A5","pred":"db_id","subj":"T5","obj":"1407192"},{"id":"A6","pred":"db_id","subj":"T6","obj":"451987"},{"id":"A7","pred":"db_id","subj":"T7","obj":"451987"},{"id":"A8","pred":"db_id","subj":"T8","obj":"209674"},{"id":"A9","pred":"db_id","subj":"T9","obj":"9606"},{"id":"A10","pred":"db_id","subj":"T10","obj":"194440"},{"id":"A11","pred":"db_id","subj":"T11","obj":"1369706"},{"id":"A12","pred":"db_id","subj":"T12","obj":"582003"},{"id":"A13","pred":"db_id","subj":"T13","obj":"451987"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"Organism-Gold","denotations":[{"id":"T1","span":{"begin":111,"end":116},"obj":"Species"},{"id":"T2","span":{"begin":1312,"end":1317},"obj":"Species"},{"id":"T3","span":{"begin":1312,"end":1346},"obj":"Species"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"9606"},{"id":"A2","pred":"db_id","subj":"T2","obj":"9606"},{"id":"A3","pred":"db_id","subj":"T3","obj":"11908"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"GlyCosmos15-CL","denotations":[{"id":"T1","span":{"begin":43,"end":54},"obj":"Cell"},{"id":"T2","span":{"begin":55,"end":65},"obj":"Cell"},{"id":"T4","span":{"begin":117,"end":124},"obj":"Cell"},{"id":"T5","span":{"begin":126,"end":137},"obj":"Cell"},{"id":"T6","span":{"begin":138,"end":148},"obj":"Cell"},{"id":"T8","span":{"begin":246,"end":253},"obj":"Cell"},{"id":"T9","span":{"begin":255,"end":266},"obj":"Cell"},{"id":"T10","span":{"begin":268,"end":279},"obj":"Cell"},{"id":"T12","span":{"begin":285,"end":302},"obj":"Cell"},{"id":"T13","span":{"begin":706,"end":713},"obj":"Cell"},{"id":"T14","span":{"begin":1318,"end":1324},"obj":"Cell"},{"id":"T15","span":{"begin":1460,"end":1467},"obj":"Cell"},{"id":"T16","span":{"begin":1581,"end":1588},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0000094"},{"id":"A2","pred":"cl_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL:0000235"},{"id":"A3","pred":"cl_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL:0000394"},{"id":"A4","pred":"cl_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/CL:0000084"},{"id":"A5","pred":"cl_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/CL:0000094"},{"id":"A6","pred":"cl_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/CL:0000235"},{"id":"A7","pred":"cl_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/CL:0000394"},{"id":"A8","pred":"cl_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/CL:0000084"},{"id":"A9","pred":"cl_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/CL:0000057"},{"id":"A10","pred":"cl_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/CL:0000235"},{"id":"A11","pred":"cl_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/CL:0000394"},{"id":"A12","pred":"cl_id","subj":"T12","obj":"http://purl.obolibrary.org/obo/CL:0000115"},{"id":"A13","pred":"cl_id","subj":"T13","obj":"http://purl.obolibrary.org/obo/CL:0000084"},{"id":"A14","pred":"cl_id","subj":"T14","obj":"http://purl.obolibrary.org/obo/CL:0000084"},{"id":"A15","pred":"cl_id","subj":"T15","obj":"http://purl.obolibrary.org/obo/CL:0000084"},{"id":"A16","pred":"cl_id","subj":"T16","obj":"http://purl.obolibrary.org/obo/CL:0000084"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"GlyCosmos15-Taxon","denotations":[{"id":"T1","span":{"begin":111,"end":116},"obj":"Organism"},{"id":"T2","span":{"begin":1312,"end":1317},"obj":"Organism"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"9606"},{"id":"A2","pred":"db_id","subj":"T2","obj":"9606"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"GlyCosmos15-UBERON","denotations":[{"id":"T1","span":{"begin":43,"end":54},"obj":"Body_part"},{"id":"T2","span":{"begin":55,"end":65},"obj":"Body_part"},{"id":"T3","span":{"begin":126,"end":137},"obj":"Body_part"},{"id":"T4","span":{"begin":138,"end":148},"obj":"Body_part"},{"id":"T5","span":{"begin":255,"end":266},"obj":"Body_part"},{"id":"T6","span":{"begin":268,"end":279},"obj":"Body_part"},{"id":"T7","span":{"begin":285,"end":302},"obj":"Body_part"},{"id":"T8","span":{"begin":763,"end":768},"obj":"Body_part"},{"id":"T9","span":{"begin":1318,"end":1324},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL_0000094"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL_0000235"},{"id":"A3","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/CL_0000094"},{"id":"A4","pred":"uberon_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/CL_0000235"},{"id":"A5","pred":"uberon_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/CL_0000057"},{"id":"A6","pred":"uberon_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/CL_0000235"},{"id":"A7","pred":"uberon_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/CL_0000115"},{"id":"A8","pred":"uberon_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/UBERON_0002488"},{"id":"A9","pred":"uberon_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/CL_0000084"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"GlyCosmos15-Sentences","blocks":[{"id":"T1","span":{"begin":0,"end":125},"obj":"Sentence"},{"id":"T2","span":{"begin":126,"end":303},"obj":"Sentence"},{"id":"T3","span":{"begin":304,"end":508},"obj":"Sentence"},{"id":"T4","span":{"begin":509,"end":714},"obj":"Sentence"},{"id":"T5","span":{"begin":715,"end":868},"obj":"Sentence"},{"id":"T6","span":{"begin":869,"end":1005},"obj":"Sentence"},{"id":"T7","span":{"begin":1006,"end":1160},"obj":"Sentence"},{"id":"T8","span":{"begin":1161,"end":1267},"obj":"Sentence"},{"id":"T9","span":{"begin":1268,"end":1468},"obj":"Sentence"},{"id":"T10","span":{"begin":1469,"end":1652},"obj":"Sentence"},{"id":"T11","span":{"begin":1653,"end":1797},"obj":"Sentence"},{"id":"T12","span":{"begin":1798,"end":1992},"obj":"Sentence"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"GlyCosmos15-MONDO","denotations":[{"id":"T1","span":{"begin":466,"end":494},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"MONDO:0011996"}],"namespaces":[{"prefix":"MONDO","uri":"http://purl.obolibrary.org/obo/MONDO_"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"GlyCosmos15-FMA","denotations":[{"id":"T1","span":{"begin":43,"end":54},"obj":"Body_part"},{"id":"T2","span":{"begin":55,"end":65},"obj":"Body_part"},{"id":"T3","span":{"begin":126,"end":137},"obj":"Body_part"},{"id":"T4","span":{"begin":138,"end":148},"obj":"Body_part"},{"id":"T5","span":{"begin":255,"end":266},"obj":"Body_part"},{"id":"T6","span":{"begin":268,"end":279},"obj":"Body_part"},{"id":"T7","span":{"begin":285,"end":302},"obj":"Body_part"},{"id":"T8","span":{"begin":763,"end":768},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"FMA:62854"},{"id":"A2","pred":"db_id","subj":"T2","obj":"FMA:63261"},{"id":"A3","pred":"db_id","subj":"T3","obj":"FMA:62854"},{"id":"A4","pred":"db_id","subj":"T4","obj":"FMA:63261"},{"id":"A5","pred":"db_id","subj":"T5","obj":"FMA:63877"},{"id":"A6","pred":"db_id","subj":"T6","obj":"FMA:63261"},{"id":"A7","pred":"db_id","subj":"T7","obj":"FMA:66772"},{"id":"A8","pred":"db_id","subj":"T8","obj":"FMA:60992"}],"namespaces":[{"prefix":"FMA","uri":"http://purl.org/sig/ont/fma/fma"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"GlyCosmos15-MAT","denotations":[{"id":"T1","span":{"begin":952,"end":960},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"mat_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MAT_0000491"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"NCBITAXON","denotations":[{"id":"T1","span":{"begin":111,"end":116},"obj":"OrganismTaxon"},{"id":"T2","span":{"begin":1312,"end":1317},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"9606"},{"id":"A2","pred":"db_id","subj":"T2","obj":"9606"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":43,"end":54},"obj":"Body_part"},{"id":"T2","span":{"begin":55,"end":65},"obj":"Body_part"},{"id":"T3","span":{"begin":126,"end":137},"obj":"Body_part"},{"id":"T4","span":{"begin":138,"end":148},"obj":"Body_part"},{"id":"T5","span":{"begin":255,"end":266},"obj":"Body_part"},{"id":"T6","span":{"begin":268,"end":279},"obj":"Body_part"},{"id":"T7","span":{"begin":285,"end":302},"obj":"Body_part"},{"id":"T8","span":{"begin":763,"end":768},"obj":"Body_part"},{"id":"T9","span":{"begin":1318,"end":1324},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL_0000094"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL_0000235"},{"id":"A3","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/CL_0000094"},{"id":"A4","pred":"uberon_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/CL_0000235"},{"id":"A5","pred":"uberon_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/CL_0000057"},{"id":"A6","pred":"uberon_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/CL_0000235"},{"id":"A7","pred":"uberon_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/CL_0000115"},{"id":"A8","pred":"uberon_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/UBERON_0002488"},{"id":"A9","pred":"uberon_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/CL_0000084"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}

{"project":"CL-cell","denotations":[{"id":"T1","span":{"begin":43,"end":54},"obj":"Cell"},{"id":"T2","span":{"begin":55,"end":65},"obj":"Cell"},{"id":"T4","span":{"begin":117,"end":124},"obj":"Cell"},{"id":"T5","span":{"begin":126,"end":137},"obj":"Cell"},{"id":"T6","span":{"begin":138,"end":148},"obj":"Cell"},{"id":"T8","span":{"begin":246,"end":253},"obj":"Cell"},{"id":"T9","span":{"begin":255,"end":266},"obj":"Cell"},{"id":"T10","span":{"begin":268,"end":279},"obj":"Cell"},{"id":"T12","span":{"begin":285,"end":302},"obj":"Cell"},{"id":"T13","span":{"begin":706,"end":713},"obj":"Cell"},{"id":"T14","span":{"begin":1318,"end":1324},"obj":"Cell"},{"id":"T15","span":{"begin":1460,"end":1467},"obj":"Cell"},{"id":"T16","span":{"begin":1581,"end":1588},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0000094"},{"id":"A2","pred":"cl_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL:0000235"},{"id":"A3","pred":"cl_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL:0000394"},{"id":"A4","pred":"cl_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/CL:0000084"},{"id":"A5","pred":"cl_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/CL:0000094"},{"id":"A6","pred":"cl_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/CL:0000235"},{"id":"A7","pred":"cl_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/CL:0000394"},{"id":"A8","pred":"cl_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/CL:0000084"},{"id":"A9","pred":"cl_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/CL:0000057"},{"id":"A10","pred":"cl_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/CL:0000235"},{"id":"A11","pred":"cl_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/CL:0000394"},{"id":"A12","pred":"cl_id","subj":"T12","obj":"http://purl.obolibrary.org/obo/CL:0000115"},{"id":"A13","pred":"cl_id","subj":"T13","obj":"http://purl.obolibrary.org/obo/CL:0000084"},{"id":"A14","pred":"cl_id","subj":"T14","obj":"http://purl.obolibrary.org/obo/CL:0000084"},{"id":"A15","pred":"cl_id","subj":"T15","obj":"http://purl.obolibrary.org/obo/CL:0000084"},{"id":"A16","pred":"cl_id","subj":"T16","obj":"http://purl.obolibrary.org/obo/CL:0000084"}],"text":"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells.\nGranulocyte-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."}