PubMed:8662666 JSON TXT

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GlyCosmos6-UBERON

GlyCosmos6-Glycan-Motif-Image

{"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."}

sentences

{"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."}

GlyCosmos6-Glycan-Motif-Structure

{"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."}

Glycosmos6-MAT

{"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."}

GlyCosmos6-CLO

mondo_disease

{"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."}

NCBITAXON

{"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":"NCBItxid:9606"},{"id":"A2","pred":"db_id","subj":"T2","obj":"NCBItxid: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."}

Inflammaging

{"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."}

DisGeNET

{"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."}

jnlpba-st-training

{"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."}

DisGeNET5_gene_disease

{"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."}

GENIAcorpus

pubmed-sentences-benchmark

{"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."}

genia-medco-coref