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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2011-7-7
pubmed:databankReference
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.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-10398197, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-10623627, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-10856157, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-11106659, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-11170002, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-11294645, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-11395412, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-11433033, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-11512661, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-12202041, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-12407101, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-12796494, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-12805549, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-15022305, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-15107489, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-15308744, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-15314653, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-15371438, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-15563464, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-15797927, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-15800630, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-16311605, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-16403635, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-16735438, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-16793062, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-16959972, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-17070642, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-17391707, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-17639082, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-17676063, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-18092005, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-18193062, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-18598942, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-18799576, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-19244240, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-19250904, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-19864417, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-19865164, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-19889764, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-20400950, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-20484370, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-20547484, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-20554522, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-3019334, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-3366776, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-4092697, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-7919794, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-8320255, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-8509422, http://linkedlifedata.com/resource/pubmed/commentcorrection/21345933-9822615
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1362-4962
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5067-81
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Nuclear protein LEDGF/p75 recognizes supercoiled DNA by a novel DNA-binding domain.
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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