ArticleNucleic acids research2011
Nuclear protein LEDGF/p75 recognizes supercoiled DNA by a novel DNA-binding domain.
Article in Nucleic acids research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 37 citations in OpenAlex.
- The Impact of Lens Epithelium-Derived Growth Factor p75 Dimerization on Its Tethering Function.Cells · 2024Article
- Selective DNA-binding of SP120 (rat ortholog of human hnRNP U) is mediated by arginine-glycine rich domain and modulated by RNA.PloS one · 2023Article
- LEDGINs, Inhibitors of the Interaction Between HIV-1 Integrase and LEDGF/p75, Are Potent Antivirals with a Potential to Cure HIV Infection.Advances in experimental medicine and biology · 2021Article
- Structure of H3K36-methylated nucleosome-PWWP complex reveals multivalent cross-gyre binding.Nature structural & molecular biology · 2020Article
- Cellular and molecular mechanisms of HIV-1 integration targeting.Cellular and molecular life sciences : CMLS · 2018Review
- Investigating DNA supercoiling in eukaryotic genomes.Briefings in functional genomics · 2017Review
- Dynamic Oligomerization of Integrase Orchestrates HIV Nuclear Entry.Scientific reports · 2016Article
- The significance of autoantibodies to DFS70/LEDGFp75 in health and disease: integrating basic science with clinical understanding.Clinical and experimental medicine · 2016Review
- Towards a Safer, More Randomized Lentiviral Vector Integration Profile Exploring Artificial LEDGF Chimeras.PloS one · 2016Article
- Lentivector integration sites in ependymal cells from a model of metachromatic leukodystrophy: non-B DNA as a new factor influencing integration.Molecular therapy. Nucleic acids · 2014Article
- Article
- Understanding lentiviral vector chromatin targeting: working to reduce insertional mutagenic potential for gene therapy.Gene therapy · 2013Review
- Nucleosomal DNA binding drives the recognition of H3K36-methylated nucleosomes by the PSIP1-PWWP domain.Epigenetics & chromatin · 2013Article
- Epigenetic repression of LEDGF during UVB exposure by recruitment of SUV39H1 and HDAC1 to the Sp1-responsive elements within LEDGF promoter CpG island.Epigenetics · 2013Article
- Discovery of novel inhibitors of LEDGF/p75-IN protein-protein interactions.Bioorganic & medicinal chemistry · 2013Article
- Lens epithelium-derived growth factor deSumoylation by Sumo-specific protease-1 regulates its transcriptional activation of small heat shock protein and the cellular response.The FEBS journal · 2012Article
- The stress oncoprotein LEDGF/p75 interacts with the methyl CpG binding protein MeCP2 and influences its transcriptional activity.Molecular cancer research : MCR · 2012Article
- Article
- Role of the PWWP domain of lens epithelium-derived growth factor (LEDGF)/p75 cofactor in lentiviral integration targeting.The Journal of biological chemistry · 2011Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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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