Fiche publication
Date publication
mars 2017
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Pr ROHR Olivier
Tous les auteurs :
Fauquenoy S, Robette G, Kula A, Vanhulle C, Bouchat S, Delacourt N, Rodari A, Marban C, Schwartz C, Burny A, Rohr O, Van Driessche B, Van Lint C
Lien Pubmed
Résumé
Human T-lymphotropic Virus type 1 (HTLV-1) infection is characterized by viral latency in the majority of infected cells and by the absence of viremia. These features are thought to be due to the repression of viral sense transcription in vivo. Here, our in silico analysis of the HTLV-1 Long Terminal Repeat (LTR) promoter nucleotide sequence revealed, in addition to the four Sp1 binding sites previously identified, the presence of two additional potential Sp1 sites within the R region. We demonstrated that the Sp1 and Sp3 transcription factors bound in vitro to these two sites and compared the binding affinity for Sp1 of all six different HTLV-1 Sp1 sites. By chromatin immunoprecipitation experiments, we showed Sp1 recruitment in vivo to the newly identified Sp1 sites. We demonstrated in the nucleosomal context of an episomal reporter vector that the Sp1 sites interfered with both the sense and antisense LTR promoter activities. Interestingly, the Sp1 sites exhibited together a repressor effect on the LTR sense transcriptional activity but had no effect on the LTR antisense activity. Thus, our results demonstrate the presence of two new functional Sp1 binding sites in the HTLV-1 LTR, which act as negative cis-regulatory elements of sense viral transcription.
Mots clés
Binding Sites, Chromatin Immunoprecipitation, Epigenetic Repression, HEK293 Cells, Host-Pathogen Interactions, Human T-lymphotropic virus 1, genetics, Humans, Jurkat Cells, Protein Binding, Sp1 Transcription Factor, metabolism, Sp3 Transcription Factor, metabolism, Terminal Repeat Sequences, Transcription, Genetic
Référence
Sci Rep. 2017 03 3;7:43221
