ArticleNucleic acids research2011
The transcriptional co-activator LEDGF/p75 displays a dynamic scan-and-lock mechanism for chromatin tethering.
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 37 papers.
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37 citing papers in PubMed, 60 citations in OpenAlex.
- Agonist-controlled competition of RAR and VDR nuclear receptors for heterodimerization with RXR is manifested in their DNA binding.The Journal of biological chemistry · 2023Article
- Hetero-pentamerization determines mobility and conductance of Glycine receptor α3 splice variants.Cellular and molecular life sciences : CMLS · 2022Article
- BET-Independent Murine Leukemia Virus Integration Is RetargetedMicrobiology spectrum · 2022Article
- Contrasting DNA-binding behaviour by ISL1 and LHX3 underpins differential gene targeting in neuronal cell specification.Journal of structural biology: X · 2021Article
- Agonist binding directs dynamic competition among nuclear receptors for heterodimerization with retinoid X receptor.The Journal of biological chemistry · 2020Article
- Structure of H3K36-methylated nucleosome-PWWP complex reveals multivalent cross-gyre binding.Nature structural & molecular biology · 2020Article
- Prototype foamy virus integrase is promiscuous for target choice.Biochemical and biophysical research communications · 2018Article
- Review
- Dynamic Oligomerization of Integrase Orchestrates HIV Nuclear Entry.Scientific reports · 2016Article
- Arbitrary-Region Raster Image Correlation Spectroscopy.Biophysical journal · 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
- Live-cell observation of cytosolic HIV-1 assembly onset reveals RNA-interacting Gag oligomers.The Journal of cell biology · 2015Article
- HIV-1 IN/Pol recruits LEDGF/p75 into viral particles.Retrovirology · 2015Article
- Psip1/Ledgf p75 restrains Hox gene expression by recruiting both trithorax and polycomb group proteins.Nucleic acids research · 2014Article
- Allosteric inhibition of human immunodeficiency virus integrase: late block during viral replication and abnormal multimerization involving specific protein domains.The Journal of biological chemistry · 2014Article
- Dynamics of the ternary complex formed by c-Myc interactor JPO2, transcriptional co-activator LEDGF/p75, and chromatin.The Journal of biological chemistry · 2014Article
- HIV virions as nanoscopic test tubes for probing oligomerization of the integrase enzyme.ACS nano · 2014Article
- Ligand binding shifts highly mobile retinoid X receptor to the chromatin-bound state in a coactivator-dependent manner, as revealed by single-cell imaging.Molecular and cellular biology · 2014Article
- GPR37 protein trafficking to the plasma membrane regulated by prosaposin and GM1 gangliosides promotes cell viability.The Journal of biological chemistry · 2014Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nearly all cellular and disease related functions of the transcriptional co-activator lens epithelium-derived growth factor (LEDGF/p75) involve tethering of interaction partners to chromatin via its conserved integrase binding domain (IBD), but little is known about the mechanism of in vivo chromatin binding and tethering. In this work we studied LEDGF/p75 in real-time in living HeLa cells combining different quantitative fluorescence techniques: spot fluorescence recovery after photobleaching (sFRAP) and half-nucleus fluorescence recovery after photobleaching (hnFRAP), continuous photobleaching, fluorescence correlation spectroscopy (FCS) and an improved FCS method to study diffusion dependence of chromatin binding, tunable focus FCS. LEDGF/p75 moves about in nuclei of living cells in a chromatin hopping/scanning mode typical for transcription factors. The PWWP domain of LEDGF/p75 is necessary, but not sufficient for in vivo chromatin binding. After interaction with HIV-1 integrase via its IBD, a general protein-protein interaction motif, kinetics of LEDGF/p75 shift to 75-fold larger affinity for chromatin. The PWWP is crucial for locking the complex on chromatin. We propose a scan-and-lock model for LEDGF/p75, unifying paradoxical notions of transcriptional co-activation and lentiviral integration targeting.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.