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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2010-2-17
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pubmed:abstractText |
Lens epithelium-derived growth factor (LEDGF) fusion proteins can direct HIV-1 DNA integration to novel sites in the host genome. The C terminus of LEDGF contains an integrase binding domain (IBD), and the N terminus binds chromatin. LEDGF normally directs integrations to the bodies of expressed genes. Replacing the N terminus of LEDGF with chromatin binding domains (CBDs) from other proteins changes the specificity of HIV-1 DNA integration. We chose two well-characterized CBDs: the plant homeodomain (PHD) finger from ING2 and the chromodomain from heterochromatin binding protein 1alpha (HP1alpha). The ING2 PHD finger binds H3K4me3, a histone mark that is associated with the transcriptional start sites of expressed genes. The HP1alpha chromodomain binds H3K9me2,3, histone marks that are widely distributed throughout the genome. A fusion protein in which the ING2 PHD finger was linked to the LEDGF IBD directed integrations near the start sites of expressed genes. A similar fusion protein in which the HP1alpha chromodomain was linked to the LEDGF IBD directed integrations to sites that differed from both the PHD finger fusion-directed and LEDGF-directed integration sites. The ability to redirect HIV-1 DNA integration may help solve the problems associated with the activation of oncogenes when retroviruses are used in gene therapy.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/20133638-11413321,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20133638-12202041,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20133638-12805549,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20133638-14564000,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/20133638-17218268,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20133638-17267494,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20133638-17409138,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/20133638-18799576,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20133638-18802438,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20133638-19132083,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20133638-19609362,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20133638-20145107,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20133638-215325,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20133638-4291934,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20133638-7769729
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1091-6490
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pubmed:author |
pubmed-author:AllisC DavidCD,
pubmed-author:EngelmanAlanA,
pubmed-author:FerrisAndrea LAL,
pubmed-author:HughesChristina MCM,
pubmed-author:HughesStephen HSH,
pubmed-author:MilneThomas ATA,
pubmed-author:ShunMing-ChiehMC,
pubmed-author:SmithSteven JSJ,
pubmed-author:StewartClaudiaC,
pubmed-author:WangGang GGG,
pubmed-author:WuXiaolinX
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pubmed:issnType |
Electronic
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pubmed:day |
16
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pubmed:volume |
107
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3135-40
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pubmed:dateRevised |
2011-3-22
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pubmed:meshHeading |
pubmed-meshheading:20133638-Animals,
pubmed-meshheading:20133638-Binding Sites,
pubmed-meshheading:20133638-Cell Line,
pubmed-meshheading:20133638-Chromatin,
pubmed-meshheading:20133638-Computational Biology,
pubmed-meshheading:20133638-DNA, Viral,
pubmed-meshheading:20133638-Flow Cytometry,
pubmed-meshheading:20133638-Gene Expression Profiling,
pubmed-meshheading:20133638-Gene Therapy,
pubmed-meshheading:20133638-HIV Integrase,
pubmed-meshheading:20133638-HIV-1,
pubmed-meshheading:20133638-Homeodomain Proteins,
pubmed-meshheading:20133638-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:20133638-Mice,
pubmed-meshheading:20133638-Mice, Knockout,
pubmed-meshheading:20133638-Protein Structure, Tertiary,
pubmed-meshheading:20133638-Sequence Analysis, DNA,
pubmed-meshheading:20133638-Tumor Suppressor Proteins,
pubmed-meshheading:20133638-Virus Integration
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pubmed:year |
2010
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