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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
29
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pubmed:dateCreated |
1993-11-18
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pubmed:abstractText |
Hypoxia-inducible factor 1 (HIF-1) is a DNA binding activity detected in nuclear extracts from Hep3B cells cultured in 1% O2 but not in extracts from cells cultured in 20% O2. HIF-1 binds to a sequence within the human erythropoietin gene enhancer that is required for hypoxic activation of transcription. Induction of HIF-1 is inhibited by cycloheximide, which also inhibits induction of erythropoietin RNA. We now demonstrate that induction of both HIF-1 and erythropoietin RNA is inhibited by the protein kinase inhibitor 2-aminopurine. HIF-1 binding to DNA was eliminated by phosphatase treatment of nuclear extracts. Actinomycin D also inhibited HIF-1 induction, suggesting that de novo transcription is required. The kinetics of HIF-1 induction by hypoxia paralleled the kinetics of erythropoietin gene transcriptional induction. HIF-1 DNA binding activity decayed rapidly when hypoxic cells were exposed to increased oxygen tension. In vitro, the kinetics of HIF-1 association with, and dissociation from, its binding site were extremely rapid, with a t1/2 for both processes of < 1 min. These findings are consistent with the proposed function of HIF-1 as a physiologic regulator of gene expression that responds to changes in cellular oxygen tension. Methylation interference analysis indicated that HIF-1 makes specific contacts with DNA in the major groove.
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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/2-Aminopurine,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Dactinomycin,
http://linkedlifedata.com/resource/pubmed/chemical/Erythropoietin,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oligodeoxyribonucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Oxygen,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoric Monoester Hydrolases,
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 |
Oct
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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 |
15
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pubmed:volume |
268
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
21513-8
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:8408001-2-Aminopurine,
pubmed-meshheading:8408001-Base Sequence,
pubmed-meshheading:8408001-Binding Sites,
pubmed-meshheading:8408001-Cell Hypoxia,
pubmed-meshheading:8408001-Cells, Cultured,
pubmed-meshheading:8408001-DNA,
pubmed-meshheading:8408001-DNA-Binding Proteins,
pubmed-meshheading:8408001-Dactinomycin,
pubmed-meshheading:8408001-Erythropoietin,
pubmed-meshheading:8408001-Hypoxia-Inducible Factor 1,
pubmed-meshheading:8408001-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:8408001-Methylation,
pubmed-meshheading:8408001-Molecular Sequence Data,
pubmed-meshheading:8408001-Nuclear Proteins,
pubmed-meshheading:8408001-Oligodeoxyribonucleotides,
pubmed-meshheading:8408001-Oxygen,
pubmed-meshheading:8408001-Phosphoric Monoester Hydrolases,
pubmed-meshheading:8408001-Protein Binding,
pubmed-meshheading:8408001-RNA, Messenger,
pubmed-meshheading:8408001-Transcription, Genetic,
pubmed-meshheading:8408001-Transcription Factors
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pubmed:year |
1993
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pubmed:articleTitle |
Characterization of hypoxia-inducible factor 1 and regulation of DNA binding activity by hypoxia.
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pubmed:affiliation |
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-3914.
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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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