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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
28
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pubmed:dateCreated |
1996-8-29
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pubmed:abstractText |
Expression of DNA topoisomerase IIalpha mRNA and protein reflects the proliferative state of mammalian cell lines and tissues with high levels in actively cycling cells but marked down-regulation during serum deprivation or cell density-induced growth arrest. Using stably integrated gene fusions comprising the human topoisomerase IIalpha promoter with a growth hormone reporter gene, we have localized elements required for the differential activity of the topoisomerase IIalpha promoter in proliferating and confluence-arrested cells. Deletion analysis localized the region of the promoter that responded to changes in the cellular growth state to between -101 and -144 base pairs. Mutation analysis identified an inverted CCAAT box (ICB) located at -108 to -104 as necessary for promoter down-regulation in confluence-arrested cells, while several other potential cis-acting elements, including four additional ICBs, were shown not to be required. The critical ICB was recognized in vitro by the CCAAT box binding factor, NF-Y, with levels of binding activity higher in extracts from proliferating cells than from confluence-arrested cells. We conclude that the differential regulation of topoisomerase IIalpha gene expression in cycling and confluence-arrested cells is mediated, at least in part, through proliferation-specific binding of factors to an ICB element in the gene promoter.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Enhancer-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Topoisomerases, Type II,
http://linkedlifedata.com/resource/pubmed/chemical/DNA topoisomerase II alpha,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
12
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pubmed:volume |
271
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
16741-7
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:8663303-3T3 Cells,
pubmed-meshheading:8663303-Animals,
pubmed-meshheading:8663303-Antigens, Neoplasm,
pubmed-meshheading:8663303-Base Sequence,
pubmed-meshheading:8663303-CCAAT-Enhancer-Binding Proteins,
pubmed-meshheading:8663303-Cell Division,
pubmed-meshheading:8663303-DNA Primers,
pubmed-meshheading:8663303-DNA Topoisomerases, Type II,
pubmed-meshheading:8663303-DNA-Binding Proteins,
pubmed-meshheading:8663303-Down-Regulation,
pubmed-meshheading:8663303-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:8663303-Genes, Reporter,
pubmed-meshheading:8663303-Growth Hormone,
pubmed-meshheading:8663303-Humans,
pubmed-meshheading:8663303-Isoenzymes,
pubmed-meshheading:8663303-Mice,
pubmed-meshheading:8663303-Molecular Sequence Data,
pubmed-meshheading:8663303-Promoter Regions, Genetic,
pubmed-meshheading:8663303-Protein Binding,
pubmed-meshheading:8663303-RNA, Messenger,
pubmed-meshheading:8663303-Transcription Factors,
pubmed-meshheading:8663303-Tumor Cells, Cultured
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pubmed:year |
1996
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pubmed:articleTitle |
Regulation of the human topoisomerase IIalpha gene promoter in confluence-arrested cells.
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pubmed:affiliation |
Imperial Cancer Research Fund Laboratories, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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