rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2011-7-7
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pubmed:databankReference |
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pubmed:abstractText |
Lens epithelium-derived growth factor (LEDGF) or p75 is a co-activator of general transcription and also involved in insertion of human immunodeficiency virus type I (HIV-1) cDNA into host cell genome, which occurs preferentially to active transcription units. These phenomena may share an underlying molecular mechanism in common. We report here that LEDGF/p75 binds negatively supercoiled DNA selectively over unconstrained DNA. We identified a novel DNA-binding domain in the protein and termed it 'supercoiled DNA-recognition domain' (SRD). Recombinant protein fragments containing SRD showed a preferential binding to supercoiled DNA in vitro. SRD harbors a characteristic cluster of lysine and glutamic/aspartic acid residues. A polypeptide mimicking the cluster (K(9)E(9)K(9)) also showed this specificity, suggesting that the cluster is an essential element for the supercoil recognition. eGFP-tagged LEDGF/p75 expressed in the nucleus distributed partially in transcriptionally active regions that were identified by immunostaining of methylated histone H3 (H3K4me3) or incorporation of Br-UTP. This pattern of localization was observed with SRD alone but abolished if the protein lacked SRD. Thus, these results imply that LEDGF/p75 guides its binding partners, including HIV-1 integrase, to the active transcription site through recognition of negative supercoils generated around it.
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pubmed:commentsCorrections |
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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 |
Jul
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pubmed:issn |
1362-4962
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pubmed:author |
|
pubmed:issnType |
Electronic
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pubmed:volume |
39
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5067-81
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pubmed:meshHeading |
pubmed-meshheading:21345933-Animals,
pubmed-meshheading:21345933-Base Sequence,
pubmed-meshheading:21345933-Cell Nucleus,
pubmed-meshheading:21345933-DNA, Superhelical,
pubmed-meshheading:21345933-HeLa Cells,
pubmed-meshheading:21345933-Humans,
pubmed-meshheading:21345933-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:21345933-Molecular Sequence Data,
pubmed-meshheading:21345933-Nuclear Proteins,
pubmed-meshheading:21345933-Protein Structure, Tertiary,
pubmed-meshheading:21345933-Rats,
pubmed-meshheading:21345933-Rats, Sprague-Dawley,
pubmed-meshheading:21345933-Transcription, Genetic
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pubmed:year |
2011
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pubmed:articleTitle |
Nuclear protein LEDGF/p75 recognizes supercoiled DNA by a novel DNA-binding domain.
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pubmed:affiliation |
Department of Neurogenomics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
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