Evidence map›Paper›PMID 37254203›Full record

ReviewRetrovirology2023

DNA topoisomerase 1 represses HIV-1 promoter activity through its interaction with a guanine quadruplex present in the LTR sequence.

María José Lista, Anne-Caroline Jousset, Mingpan Cheng, Violaine Saint-André, Elouan Perrot, Melissa Rodrigues, Carmelo Di Primo, Danielle Gadelle, Elenia Toccafondi, Emmanuel Segeral and 4 more

Erratum issuedOpen access · goldAbstract readReview
In one paragraph

Review in Retrovirology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

6 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. The Role of Tumor Stem Cells in Colorectal Cancer Drug Resistance.Cancer control : journal of the Moffitt Cancer Center
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 7 institutions in 3 countries.

María José ListaUniversité Paris Cité, Institut Cochin, INSERM, CNRS, F-75014, Paris, France.
Anne-Caroline JoussetUniversité Paris Cité, Institut Cochin, INSERM, CNRS, F-75014, Paris, France.
Mingpan ChengCNRS UMR 5320, INSERM U1212, ARNA, Univ. Bordeaux, IECB, 33000, Bordeaux, France.
Violaine Saint-AndréInstitut Pasteur, Bioinformatics and Biostatistics Hub, Université Paris Cité, 75015, Paris, France.
Elouan PerrotInstitut Pasteur, Departement of Virology, Université Paris Cité, 75015, Paris, France.
Melissa RodriguesInstitut Pasteur, Departement of Virology, Université Paris Cité, 75015, Paris, France.
Carmelo Di PrimoCNRS UMR 5320, INSERM U1212, ARNA, Univ. Bordeaux, IECB, 33000, Bordeaux, France.
Danielle GadelleInstitut de Biologie Integrative de la Cellule, CNRS, Université Paris-Saclay, 91198, Gif Sur Yvette, Cedex, France.
Elenia ToccafondiUniversité Paris Cité, Institut Cochin, INSERM, CNRS, F-75014, Paris, France.
Emmanuel SegeralUniversité Paris Cité, Institut Cochin, INSERM, CNRS, F-75014, Paris, France.
Clarisse Berlioz-TorrentUniversité Paris Cité, Institut Cochin, INSERM, CNRS, F-75014, Paris, France.
Stéphane EmilianiUniversité Paris Cité, Institut Cochin, INSERM, CNRS, F-75014, Paris, France.
Jean-Louis MergnyCNRS UMR 5320, INSERM U1212, ARNA, Univ. Bordeaux, IECB, 33000, Bordeaux, France.
Marc LavigneUniversité Paris Cité, Institut Cochin, INSERM, CNRS, F-75014, Paris, France. marc.lavigne@pasteur.fr.
Institut Cochin · FRDepartment of Virology · FRCentre National de la Recherche Scientifique · FRÉcole Polytechnique · FRInstitut Pasteur · FRRégulations Naturelle et Artificielle · FRUniversité de Bordeaux · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundOnce integrated in the genome of infected cells, HIV-1 provirus is transcribed by the cellular transcription machinery. This process is regulated by both viral and cellular factors, which are necessary for an efficient viral replication as well as for the setting up of viral latency, leading to a repressed transcription of the integrated provirus.

resultsIn this study, we examined the role of two parameters in HIV-1 LTR promoter activity. We identified DNA topoisomerase1 (TOP1) to be a potent repressor of this promoter and linked this repression to its catalytic domain. Additionally, we confirmed the folding of a Guanine quadruplex (G4) structure in the HIV-1 promoter and its repressive effect. We demonstrated a direct interaction between TOP1 and this G4 structure, providing evidence of a functional relationship between the two repressive elements. Mutations abolishing G4 folding affected TOP1/G4 interaction and hindered G4-dependent inhibition of TOP1 catalytic activity in vitro. As a result, HIV-1 promoter activity was reactivated in a native chromatin environment. Lastly, we noticed an enrichment of predicted G4 sequences in the promoter of TOP1-repressed cellular genes.

conclusionsOur results demonstrate the formation of a TOP1/G4 complex on the HIV-1 LTR promoter and its repressive effect on the promoter activity. They reveal the existence of a new mechanism of TOP1/G4-dependent transcriptional repression conserved between viral and human genes. This mechanism contrasts with the known property of TOP1 as global transcriptional activator and offers new perspectives for anti-cancer and anti-viral strategies.

Indexed as

HIV-1ChromatinGuanineHIV Long Terminal RepeatHumansTranscription FactorsTranscription, GeneticChromatinGuanineTranscription FactorsDNA topoisomerasesGuanine quadruplexHIV-1 latencyHIV-1 LTR promoterHIV-1 transcriptionHost-virus interactionTranscriptional regulation

Identifiers

PMID37254203
PMCPMC10228017
OpenAlexW4378782953

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.