DNA topoisomerase 1 represses HIV-1 promoter activity through its interaction with a guanine quadruplex present in the LTR sequence - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Retrovirology Année : 2023

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

Résumé

Background: 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. Results: 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. Conclusions: 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.
Fichier principal
Vignette du fichier
islandora_164796.pdf (3.11 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Licence : CC BY - Paternité

Dates et versions

hal-04136961 , version 1 (21-06-2023)

Licence

Paternité

Identifiants

Citer

María José Lista, Anne-Caroline Jousset, Mingpan Cheng, Violaine Saint-André, Elouan Perrot, et al.. DNA topoisomerase 1 represses HIV-1 promoter activity through its interaction with a guanine quadruplex present in the LTR sequence. Retrovirology, 2023, 20 (1), pp.10. ⟨10.1186/s12977-023-00625-8⟩. ⟨hal-04136961⟩
26 Consultations
7 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More