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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1993-10-15
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pubmed:abstractText |
The human c-sis gene encodes the B chain of platelet-derived growth factor (PDGF), a potent mitogen for cultured cells of mesenchymal origin. PDGF is stored in the alpha-granules of blood platelets, which are derived from bone marrow megakaryocytes and lack transcriptional machinery. Human myeloid leukemia cell line K562 can be used as a model for megakaryocytes. Phorbol-ester-mediated megakaryocytic differentiation of K562 cells is accompanied by more than 200-fold increase in the c-sis mRNA level. We have now localized transcriptional enhancers at -8.6 kb and -9.9 kb relative to the human c-sis gene transcription start site. The enhancer at -8.6 kb increases activity of the c-sis promoter by 40-60-fold specifically in K562 cells and comaps with a DNase-I-hypersensitivity (DH) site. The enhancer at -9.9 kb increases c-sis promoter activity by 5-10-fold in K562 cells and DH at that site accompanies phorbol-ester-induced megakaryocytic differentiation. In phorbol-ester-treated K562 cells the two enhancers may be negatively influenced by a silencer that comaps with DH at -10.7/-11.0 kb. Reporter gene analysis predicted that combined activity of the upstream enhancers and the c-sis promoter may result in 100-1000-fold higher promoter activity in phorbol-ester-treated K562 cells compared with untreated cells, which can fully explain the more than 200-fold increase in c-sis mRNA level. DH at -8.6 kb and -9.9 kb was also detected in human fibroblasts and in the carcinoma cell lines HeLa and PC3, which express, respectively, undetectable, low and high levels of c-sis mRNA. Although the individual DH sites displayed 4-10-fold enhancer activity in all these cells, they lost most of their biological activity when combined in a larger fragment. In addition we localized (part of) a new transcription unit at approximately 13 kb upstream of the c-sis transcription start site. The corresponding 0.45-kb sis upstream region (sur) transcript is constitutively expressed in all cell lines examined. The expression of the sur transcript is independent of the expression of c-sis mRNA and of the pattern of DH sites far upstream of the c-sis gene. Thus, at present, there is no indication that the upstream DH sites are involved in regulation of expression of the sur gene.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Deoxyribonuclease I,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet-Derived Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-sis,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0014-2956
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
216
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pubmed:geneSymbol |
PDGF-B,
c-sis
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
487-95
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:8375387-Cell Line,
pubmed-meshheading:8375387-Chromosome Mapping,
pubmed-meshheading:8375387-Deoxyribonuclease I,
pubmed-meshheading:8375387-Enhancer Elements, Genetic,
pubmed-meshheading:8375387-Exons,
pubmed-meshheading:8375387-Humans,
pubmed-meshheading:8375387-Platelet-Derived Growth Factor,
pubmed-meshheading:8375387-Promoter Regions, Genetic,
pubmed-meshheading:8375387-Protein-Tyrosine Kinases,
pubmed-meshheading:8375387-Proto-Oncogene Proteins,
pubmed-meshheading:8375387-Proto-Oncogene Proteins c-sis,
pubmed-meshheading:8375387-RNA, Messenger,
pubmed-meshheading:8375387-Tetradecanoylphorbol Acetate,
pubmed-meshheading:8375387-Trans-Activators,
pubmed-meshheading:8375387-Transcription, Genetic
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pubmed:year |
1993
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pubmed:articleTitle |
DNase-I-hypersensitive sites located far upstream of the human c-sis/PDGF-B gene comap with transcriptional enhancers and a silencer and are preceded by (part of) a new transcription unit.
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pubmed:affiliation |
Department of Biochemistry, University of Nijmegen, The Netherlands.
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pubmed:publicationType |
Journal Article
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