rdf:type |
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lifeskim:mentions |
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pubmed:issue |
45
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pubmed:dateCreated |
2004-11-1
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pubmed:abstractText |
Upon hypoxia, the human erythropoietin (EPO) gene is transactivated by the heterodimeric hypoxia-inducible factor 1 (HIF-1). Mammalian SWI/SNF is a chromatin-remodeling complex involved in the modulation of gene expression. We demonstrate that Brahma (Brm) and Brahma/SWI2-related gene 1 (Brg-1), alternative ATPase subunits of SWI/SNF, potentiate reporter gene activation mediated by HIF-1 in an ATPase-dependent manner. Brm was more potent than Brg-1 in the reporter gene assays. Simultaneous depletion of both Brm and Brg-1 by small interfering RNAs significantly compromised the transcription of the endogenous EPO gene triggered by hypoxia. Whereas knocking down Brm alone resulted in a moderate reduction in transcription of the EPO gene, depletion of Brg-1 resulted in an augmentation of transcription of both the EPO gene and the Brm gene, indicating that Brm can compensate for loss of Brg-1. Chromatin immunoprecipitation (ChIP) and sequential ChIP (re-ChIP) analysis showed that both Brm and Brg-1 associate with the enhancer region of the EPO gene in vivo in a hypoxia-dependent fashion and that each is present in a complex with HIF-1. Brm and Brg-1 were also recruited to the promoter of the vascular endothelial growth factor (VEGF) gene in a hypoxia-dependent fashion, although hypoxic induction of VEGF transcription was not affected by depletions of either or both Brm and Brg-1. Together these studies reveal a novel role for SWI/SNF in the activation of transcription of the EPO gene, indicate an important communication and compensation between Brm and Brg-1, and suggest that the requirement for SWI/SNF during hypoxic induction is gene-specific.
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pubmed:grant |
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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/3' Untranslated Regions,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Chromatin,
http://linkedlifedata.com/resource/pubmed/chemical/Cross-Linking Reagents,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Helicases,
http://linkedlifedata.com/resource/pubmed/chemical/Drosophila Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Erythropoietin,
http://linkedlifedata.com/resource/pubmed/chemical/Histones,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oxygen,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/SMARCA4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A,
http://linkedlifedata.com/resource/pubmed/chemical/brm protein, Drosophila
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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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 |
5
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
46733-41
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pubmed:dateRevised |
2010-8-9
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pubmed:meshHeading |
pubmed-meshheading:15347669-3' Untranslated Regions,
pubmed-meshheading:15347669-Anoxia,
pubmed-meshheading:15347669-Cell Cycle Proteins,
pubmed-meshheading:15347669-Cell Line,
pubmed-meshheading:15347669-Cell Line, Tumor,
pubmed-meshheading:15347669-Chromatin,
pubmed-meshheading:15347669-Cross-Linking Reagents,
pubmed-meshheading:15347669-DNA Helicases,
pubmed-meshheading:15347669-Dimerization,
pubmed-meshheading:15347669-Drosophila Proteins,
pubmed-meshheading:15347669-Enhancer Elements, Genetic,
pubmed-meshheading:15347669-Erythropoietin,
pubmed-meshheading:15347669-Genes, Reporter,
pubmed-meshheading:15347669-Genetic Vectors,
pubmed-meshheading:15347669-Histones,
pubmed-meshheading:15347669-Humans,
pubmed-meshheading:15347669-Immunoprecipitation,
pubmed-meshheading:15347669-Luciferases,
pubmed-meshheading:15347669-Models, Genetic,
pubmed-meshheading:15347669-Nuclear Proteins,
pubmed-meshheading:15347669-Oxygen,
pubmed-meshheading:15347669-Plasmids,
pubmed-meshheading:15347669-RNA, Small Interfering,
pubmed-meshheading:15347669-RNA Interference,
pubmed-meshheading:15347669-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:15347669-Trans-Activators,
pubmed-meshheading:15347669-Transcription, Genetic,
pubmed-meshheading:15347669-Transcription Factors,
pubmed-meshheading:15347669-Transcriptional Activation,
pubmed-meshheading:15347669-Transfection,
pubmed-meshheading:15347669-Vascular Endothelial Growth Factor A
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pubmed:year |
2004
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pubmed:articleTitle |
Roles of Brahma and Brahma/SWI2-related gene 1 in hypoxic induction of the erythropoietin gene.
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pubmed:affiliation |
Department of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, Molecular Biology Institute, UCLA, Los Angeles, California 90095, 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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