Reference : LSD1 cooperates with CTIP2 to promote HIV-1 transcriptional silencing.
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
LSD1 cooperates with CTIP2 to promote HIV-1 transcriptional silencing.
Le Douce, Valentin [> >]
Colin, Laurence [> >]
Redel, Laetitia [> >]
Cherrier, Thomas mailto [Université de Liège - ULiège > Chimie et bio-industries > Biologie cell. et moléc. >]
Herbein, Georges [> >]
Aunis, Dominique [> >]
Rohr, Olivier [> >]
Van Lint, Carine [> >]
Schwartz, Christian [> >]
Nucleic Acids Research
Yes (verified by ORBi)
United Kingdom
[en] Cell Line ; Cell Nucleus/chemistry/virology ; Epigenesis, Genetic ; Gene Silencing ; HIV Long Terminal Repeat ; HIV-1/genetics/physiology ; Histone Demethylases/analysis/metabolism ; Histone-Lysine N-Methyltransferase/metabolism ; Histones/metabolism ; Humans ; Methylation ; Microglia/virology ; Promoter Regions, Genetic ; Repressor Proteins/analysis/metabolism ; Transcription, Genetic ; Tumor Suppressor Proteins/analysis/metabolism ; Virus Replication ; tat Gene Products, Human Immunodeficiency Virus/analysis
[en] 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.

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