Evidence map›Paper›PMID 34634812›Full record

ArticleNucleic acids research2021

Modulation of the intrinsic chromatin binding property of HIV-1 integrase by LEDGF/p75.

Delphine Lapaillerie, Benoît Lelandais, Eric Mauro, Floriane Lagadec, Camille Tumiotto, Csaba Miskey, Guillaume Ferran, Natacha Kuschner, Christina Calmels, Mathieu Métifiot and 7 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.7field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 18 citations in OpenAlex.

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  7. Structural rearrangements in the nucleus localize latent HIV proviruses to a perinucleolar compartment supportive of reactivation.Proceedings of the National Academy of Sciences of the United States of America · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 4 institutions in 2 countries.

Delphine LapaillerieFundamental Microbiology and Pathogenicity Lab (MFP), UMR 5234 CNRS-University of Bordeaux, SFR TransBioMed. Bordeaux, France.
Benoît LelandaisImaging and modeling unit, Computational Biology Department, Institut Pasteur, Paris, France.
Eric MauroFundamental Microbiology and Pathogenicity Lab (MFP), UMR 5234 CNRS-University of Bordeaux, SFR TransBioMed. Bordeaux, France.
Floriane LagadecFundamental Microbiology and Pathogenicity Lab (MFP), UMR 5234 CNRS-University of Bordeaux, SFR TransBioMed. Bordeaux, France.
Camille TumiottoFundamental Microbiology and Pathogenicity Lab (MFP), UMR 5234 CNRS-University of Bordeaux, SFR TransBioMed. Bordeaux, France.
Csaba MiskeyPaul-Ehrlich-Institute, division of medical biotechnology, Langen, Germany.
Guillaume FerranCHU de Bordeaux, Service de Génétique Médicale, Bordeaux France.
Natacha KuschnerCHU de Bordeaux, Service de Génétique Médicale, Bordeaux France.
Christina CalmelsFundamental Microbiology and Pathogenicity Lab (MFP), UMR 5234 CNRS-University of Bordeaux, SFR TransBioMed. Bordeaux, France.
Mathieu MétifiotFundamental Microbiology and Pathogenicity Lab (MFP), UMR 5234 CNRS-University of Bordeaux, SFR TransBioMed. Bordeaux, France.
Caroline RooryckCHU de Bordeaux, Service de Génétique Médicale, Bordeaux France.
Zoltan IvicsPaul-Ehrlich-Institute, division of medical biotechnology, Langen, Germany.
Marc RuffIGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), Département de Biologie Structurale intégrative, UDS, U596 INSERM, UMR7104, CNRS, Strasbourg, France.
Christophe ZimmerImaging and modeling unit, Computational Biology Department, Institut Pasteur, Paris, France.
Paul LesbatsFundamental Microbiology and Pathogenicity Lab (MFP), UMR 5234 CNRS-University of Bordeaux, SFR TransBioMed. Bordeaux, France.
Jérôme ToutainCHU de Bordeaux, Service de Génétique Médicale, Bordeaux France.
Vincent ParissiFundamental Microbiology and Pathogenicity Lab (MFP), UMR 5234 CNRS-University of Bordeaux, SFR TransBioMed. Bordeaux, France.ORCID 0000-0003-1661-7841
Centre National de la Recherche Scientifique · FRCentre Hospitalier Universitaire de Bordeaux · FRInstitut Pasteur · FRPaul Ehrlich Institut · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The stable insertion of the retroviral genome into the host chromosomes requires the association between integration complexes and cellular chromatin via the interaction between retroviral integrase and the nucleosomal target DNA. This final association may involve the chromatin-binding properties of both the retroviral integrase and its cellular cofactor LEDGF/p75. To investigate this and better understand the LEDGF/p75-mediated chromatin tethering of HIV-1 integrase, we used a combination of biochemical and chromosome-binding assays. Our study revealed that retroviral integrase has an intrinsic ability to bind and recognize specific chromatin regions in metaphase even in the absence of its cofactor. Furthermore, this integrase chromatin-binding property was modulated by the interaction with its cofactor LEDGF/p75, which redirected the enzyme to alternative chromosome regions. We also better determined the chromatin features recognized by each partner alone or within the functional intasome, as well as the chronology of efficient LEDGF/p75-mediated targeting of HIV-1 integrase to chromatin. Our data support a new chromatin-binding function of integrase acting in concert with LEDGF/p75 for the optimal association with the nucleosomal substrate. This work also provides additional information about the behavior of retroviral integration complexes in metaphase chromatin and the mechanism of action of LEDGF/p75 in this specific context.

Indexed as

Adaptor Proteins, Signal TransducingChromatinCloning, MolecularEscherichia coliGene ExpressionGene Expression RegulationGenetic VectorsHistonesHIV IntegraseHost-Pathogen InteractionsHumansK562 CellsPrimary Cell CultureProtein BindingProtein IsoformsRecombinant ProteinsAdaptor Proteins, Signal TransducingChromatinHistonesHIV Integrasep31 integrase protein, Human immunodeficiency virus 1Protein IsoformsPSIP1 protein, humanRecombinant ProteinsTranscription Factors

Identifiers

PMID34634812
PMCPMC8565322
OpenAlexW3206419320

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

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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.