Source:http://linkedlifedata.com/resource/pubmed/id/11463861
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
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pubmed:dateCreated |
2001-7-20
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pubmed:abstractText |
A new human GR gene sequence (hGR 1Ap/e), which is distinct from the previously identified human GR promoter and coding sequences, has been isolated and characterized. The hGR 1Ap/e sequence is approximately 31 kbp upstream of the human GR coding sequence. This sequence (2,056 bp) contains a novel promoter (the hGR 1A promoter; 1,075 bp) and untranslated exon sequence (hGR exon 1A sequence; 981 bp). Alternative splicing produces three different hGR 1A-containing transcripts, 1A1, 1A2, and 1A3. GR transcripts containing exon 1A1, 1A2, 1B, and 1C are expressed at various levels in many cancer cell lines, while the exon 1A3-containing GR transcript is expressed most abundantly in blood cell cancer cell lines. Glucocorticoid hormone treatment causes an up-regulation of exon 1A3-containing GR transcripts in CEM-C7 T-lymphoblast cells and a down-regulation of exon 1A3-containing transcripts in IM-9 B-lymphoma cells. Deoxyribonuclease I footprinting using CEM-C7 cell nuclear extract reveals four footprints in the promoter region and two intraexonic footprints. Much of the basal promoter-activating function is found in the +41/+269 sequence, which contains two deoxyribonuclease I footprints (FP5 and FP6). When this sequence is cloned into the pXP-1 luciferase reporter gene, hormone treatment causes a significant increase in luciferase activity in Jurkat T cells that are cotransfected with a GR expression vector. FP5 is an interferon regulatory factor-binding element, and it contributes significantly to basal transcription rate, but it is not activated by steroid. FP6 resembles a glucocorticoid response element and can bind GRbeta. This novel hGR 1Ap/e sequence may have future applications for the diagnosis, prognosis, and treatment of T-cell leukemia and lymphoma.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxyribonuclease I,
http://linkedlifedata.com/resource/pubmed/chemical/Glucocorticoids,
http://linkedlifedata.com/resource/pubmed/chemical/IRF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factor-1,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Glucocorticoid,
http://linkedlifedata.com/resource/pubmed/chemical/Untranslated Regions
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0888-8809
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
15
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1381-95
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:11463861-Alternative Splicing,
pubmed-meshheading:11463861-Base Sequence,
pubmed-meshheading:11463861-DNA Footprinting,
pubmed-meshheading:11463861-DNA-Binding Proteins,
pubmed-meshheading:11463861-Deoxyribonuclease I,
pubmed-meshheading:11463861-Exons,
pubmed-meshheading:11463861-Gene Expression,
pubmed-meshheading:11463861-Glucocorticoids,
pubmed-meshheading:11463861-Hematologic Neoplasms,
pubmed-meshheading:11463861-Humans,
pubmed-meshheading:11463861-Interferon Regulatory Factor-1,
pubmed-meshheading:11463861-Jurkat Cells,
pubmed-meshheading:11463861-Lymphoma, B-Cell,
pubmed-meshheading:11463861-Molecular Sequence Data,
pubmed-meshheading:11463861-Mutagenesis, Site-Directed,
pubmed-meshheading:11463861-Neoplasms,
pubmed-meshheading:11463861-Phosphoproteins,
pubmed-meshheading:11463861-Polymerase Chain Reaction,
pubmed-meshheading:11463861-Precursor Cell Lymphoblastic Leukemia-Lymphoma,
pubmed-meshheading:11463861-Promoter Regions, Genetic,
pubmed-meshheading:11463861-RNA, Messenger,
pubmed-meshheading:11463861-Receptors, Glucocorticoid,
pubmed-meshheading:11463861-Response Elements,
pubmed-meshheading:11463861-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:11463861-Transfection,
pubmed-meshheading:11463861-Tumor Cells, Cultured,
pubmed-meshheading:11463861-Untranslated Regions
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pubmed:year |
2001
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pubmed:articleTitle |
Multiple promoters exist in the human GR gene, one of which is activated by glucocorticoids.
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pubmed:affiliation |
Department of Biochemistry and Molecular Biology and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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