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

Overview of attention for article published in Retrovirology, May 2023
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  • Good Attention Score compared to outputs of the same age (69th percentile)
  • Good Attention Score compared to outputs of the same age and source (75th percentile)

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Title
DNA topoisomerase 1 represses HIV-1 promoter activity through its interaction with a guanine quadruplex present in the LTR sequence
Published in
Retrovirology, May 2023
DOI 10.1186/s12977-023-00625-8
Pubmed ID
Authors

María José Lista, Anne-Caroline Jousset, Mingpan Cheng, Violaine Saint-André, Elouan Perrot, Melissa Rodrigues, Carmelo Di Primo, Danielle Gadelle, Elenia Toccafondi, Emmanuel Segeral, Clarisse Berlioz-Torrent, Stéphane Emiliani, Jean-Louis Mergny, Marc Lavigne

Abstract

Once 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. In 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. Our 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.

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The data shown below were collected from the profiles of 7 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 3 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 3 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 2 67%
Unknown 1 33%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 2 67%
Unknown 1 33%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 20 January 2024.
All research outputs
#7,230,578
of 25,443,857 outputs
Outputs from Retrovirology
#364
of 1,275 outputs
Outputs of similar age
#120,069
of 389,212 outputs
Outputs of similar age from Retrovirology
#3
of 8 outputs
Altmetric has tracked 25,443,857 research outputs across all sources so far. This one has received more attention than most of these and is in the 71st percentile.
So far Altmetric has tracked 1,275 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.7. This one has gotten more attention than average, scoring higher than 70% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 389,212 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 69% of its contemporaries.
We're also able to compare this research output to 8 others from the same source and published within six weeks on either side of this one. This one has scored higher than 5 of them.