Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
45
pubmed:dateCreated
2004-11-1
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
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
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
46733-41
pubmed:dateRevised
2010-8-9
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
pubmed:year
2004
pubmed:articleTitle
Roles of Brahma and Brahma/SWI2-related gene 1 in hypoxic induction of the erythropoietin gene.
pubmed:affiliation
Department of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, Molecular Biology Institute, UCLA, Los Angeles, California 90095, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't