HIC1 controls cellular- and HIV-1- gene transcription via interactions with CTIP2 and HMGA1.
Fiche publication
Date publication
octobre 2016
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Pr ROHR Olivier
Tous les auteurs :
Le Douce V, Forouzanfar F, Eilebrecht S, Van Driessche B, Ait-Ammar A, Verdikt R, Kurashige Y, Marban C, Gautier V, Candolfi E, Benecke AG, Van Lint C, Rohr O, Schwartz C
Lien Pubmed
Résumé
Among many cellular transcriptional regulators, Bcl11b/CTIP2 and HGMA1 have been described to control the establishment and the persistence of HIV-1 latency in microglial cells, the main viral reservoir in the brain. In this present work, we identify and characterize a transcription factor i.e. HIC1, which physically interacts with both Bcl11b/CTIP2 and HMGA1 to co-regulate specific subsets of cellular genes and the viral HIV-1 gene. Our results suggest that HIC1 represses Tat dependent HIV-1 transcription. Interestingly, this repression of Tat function is linked to HIC1 K314 acetylation status and to SIRT1 deacetylase activity. Finally, we show that HIC1 interacts and cooperates with HGMA1 to regulate Tat dependent HIV-1 transcription. Our results also suggest that HIC1 repression of Tat function happens in a TAR dependent manner and that this TAR element may serve as HIC1 reservoir at the viral promoter to facilitate HIC1/TAT interaction.
Mots clés
Cells, Cultured, HIV-1, genetics, HMGA1a Protein, metabolism, Humans, Kruppel-Like Transcription Factors, metabolism, Neuroglia, virology, Repressor Proteins, metabolism, Transcription, Genetic, Tumor Suppressor Proteins, metabolism, tat Gene Products, Human Immunodeficiency Virus, genetics
Référence
Sci Rep. 2016 10 11;6:34920