Fiche publication


Date publication

mars 2012

Journal

Nucleic acids research

Auteurs

Membres identifiés du Cancéropôle Est :
Pr HERBEIN Georges , Pr ROHR Olivier


Tous les auteurs :
Le Douce V, Colin L, Redel L, Cherrier T, Herbein G, Aunis D, Rohr O, Van Lint C, Schwartz C

Résumé

Microglial cells are the main HIV-1 targets in the central nervous system (CNS) and constitute an important reservoir of latently infected cells. Establishment and persistence of these reservoirs rely on the chromatin structure of the integrated proviruses. We have previously demonstrated that the cellular cofactor CTIP2 forces heterochromatin formation and HIV-1 gene silencing by recruiting HDAC and HMT activities at the integrated viral promoter. In the present work, we report that the histone demethylase LSD1 represses HIV-1 transcription and viral expression in a synergistic manner with CTIP2. We show that recruitment of LSD1 at the HIV-1 proximal promoter is associated with both H3K4me3 and H3K9me3 epigenetic marks. Finally, our data suggest that LSD1-induced H3K4 trimethylation is linked to hSET1 recruitment at the integrated provirus.

Mots clés

Cell Line, Cell Nucleus, chemistry, Epigenesis, Genetic, Gene Silencing, HIV Long Terminal Repeat, HIV-1, genetics, Histone Demethylases, analysis, Histone-Lysine N-Methyltransferase, metabolism, Histones, metabolism, Humans, Methylation, Microglia, virology, Promoter Regions, Genetic, Repressor Proteins, analysis, Transcription, Genetic, Tumor Suppressor Proteins, analysis, Virus Replication, tat Gene Products, Human Immunodeficiency Virus, analysis

Référence

Nucleic Acids Res.. 2012 Mar;40(5):1904-15