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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
26
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pubmed:dateCreated |
2000-1-27
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pubmed:abstractText |
The granulocyte-macrophage colony-stimulating factor (GM-CSF) gene is part of a cytokine gene cluster and is directly linked to a conserved upstream inducible enhancer. Here we examined the in vitro and in vivo functions of the human GM-CSF enhancer and found that it was required for the correctly regulated expression of the GM-CSF gene. An inducible DNase I-hypersensitive site appeared within the enhancer in cell types such as T cells, myeloid cells, and endothelial cells that express GM-CSF, but not in nonexpressing cells. In a panel of transfected cells the human GM-CSF enhancer was activated in a tissue-specific manner in parallel with the endogenous gene. The in vivo function of the enhancer was examined in a transgenic mouse model that also addressed the issue of whether the GM-CSF locus was correctly regulated in isolation from other segments of the cytokine gene cluster. After correction for copy number the mean level of human GM-CSF expression in splenocytes from 11 lines of transgenic mice containing a 10.5-kb human GM-CSF transgene was indistinguishable from mouse GM-CSF expression (99% +/- 56% SD). In contrast, a 9.8-kb transgene lacking just the enhancer had a significantly reduced (P = 0.004) and more variable level of activity (29% +/- 89% SD). From these studies we conclude that the GM-CSF enhancer is required for the correct copy number-dependent expression of the human GM-CSF gene and that the GM-CSF gene is regulated independently from DNA elements associated with the closely linked IL-3 gene or other members of the cytokine gene cluster.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10611344-1695008,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10611344-2253879,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10611344-2549855,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10611344-2833332,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10611344-3490669,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10611344-3690667,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10611344-7545467,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10611344-7602099,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10611344-7891702,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10611344-8068174,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10611344-8246960,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10611344-8460159,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10611344-8662845,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10611344-8809409,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10611344-8934574,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10611344-9047239,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10611344-9149945,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10611344-9814700
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
21
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pubmed:volume |
96
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
15097-102
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:10611344-Animals,
pubmed-meshheading:10611344-Binding Sites,
pubmed-meshheading:10611344-Chromatin,
pubmed-meshheading:10611344-Cytokines,
pubmed-meshheading:10611344-DNA Footprinting,
pubmed-meshheading:10611344-Deoxyribonuclease I,
pubmed-meshheading:10611344-Enhancer Elements, Genetic,
pubmed-meshheading:10611344-Gene Dosage,
pubmed-meshheading:10611344-Gene Expression Regulation,
pubmed-meshheading:10611344-Granulocyte-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:10611344-HeLa Cells,
pubmed-meshheading:10611344-Humans,
pubmed-meshheading:10611344-Interleukin-3,
pubmed-meshheading:10611344-Jurkat Cells,
pubmed-meshheading:10611344-Mice,
pubmed-meshheading:10611344-Mice, Transgenic,
pubmed-meshheading:10611344-Multigene Family,
pubmed-meshheading:10611344-Tissue Distribution,
pubmed-meshheading:10611344-U937 Cells
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pubmed:year |
1999
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pubmed:articleTitle |
The human granulocyte-macrophage colony-stimulating factor gene is autonomously regulated in vivo by an inducible tissue-specific enhancer.
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pubmed:affiliation |
Division of Human Immunology, Hanson Centre For Cancer Research, Institute for Medical and Veterinary Science, Frome Road, Adelaide 5000, Australia. peter.cockerill@imvs.sa.gov.au
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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