title: LSD1 cooperates with CTIP2 to promote HIV-1 transcriptional silencing.
abstract: 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.
authors: University of Strasbourg, EA4438, Institute of parasitology, Strasbourg, France.
authors: Valentin
authors: V
authors: Le Douce
authors: Laurence
authors: L
authors: Colin
authors: Laetitia
authors: L
authors: Redel
authors: Thomas
authors: T
authors: Cherrier
authors: Georges
authors: G
authors: Herbein
authors: Dominique
authors: D
authors: Aunis
authors: Olivier
authors: O
authors: Rohr
authors: Carine
authors: C
authors: Van Lint
authors: Christian
authors: C
authors: Schwartz
mesh_terms: D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry / Q000821:virology; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D056466:Histone Demethylases / Q000032:analysis / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008745:Methylation; D017628:Microglia / Q000821:virology*; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000032:analysis / Q000378:metabolism*; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000378:metabolism*; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000032:analysis
chemical_list: C479740:BCL11B protein, human; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; C502547:WDR5 protein, human; D054322:tat Gene Products, Human Immunodeficiency Virus; D056466:Histone Demethylases; C495195:KDM1A protein, human; D011495:Histone-Lysine N-Methyltransferase; C526068:Setd1A protein, human