title: COUP-TF interacting protein 2 represses the initial phase of HIV-1 gene transcription in human microglial cells.
abstract: Human immunodeficiency virus type 1 (HIV-1) gene transcription is characterized by two temporally distinct phases. While the initial phase relies solely on cellular transcription factors, the subsequent phase is activated by the viral Tat transactivator. We have previously reported that the subsequent phase of viral gene transcription can be repressed by the chicken ovalbumin upstream promoter transcription factor (COUP-TF)-interacting protein 2 (CTIP2) in human microglial cells [O. Rohr, D. Lecestre, S. Chasserot-Golaz, C. Marban, D. Avram, D. Aunis, M. Leid and E. Schaeffer (2003), J. Virol., 77, 5415-5427]. Here, we demonstrate that CTIP proteins also repress the initial phase of HIV-1 gene transcription, mainly supported by the cellular transcription factors Sp1 and COUP-TF in microglial cells. We report that CTIP2 represses Sp1- and COUP-TF-mediated activation of HIV-1 gene transcription and viral replication as a result of physical interactions with COUP-TF and Sp1 in microglial nuclei. Using laser confocal microscopy CTIP2 was found to colocalize with Sp1, COUP-TF and the heterochromatin-associated protein Hp1alpha, which is mainly detected in transcriptionally repressed heterochromatic region. Moreover, we describe that CTIP2 can be recruited to the HIV-1 promoter via its association with Sp1 bound to the GC-box sequences of the long terminal repeat (LTR). Since our findings demonstrate that CTIP2 interacts with the HIV-1 proximal promoter, it is likely that CTIP2 promotes HIV-1 gene silencing by forcing transcriptionally repressed heterochromatic environment to the viral LTR region.
authors.affiliation: INSERM unité 575 Pathophysiology of Nervous System, Centre de Neurochimie 5 rue Blaise Pascal, 67084 Strasbourg, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Marban
authors.forename: Laetitia
authors.initials: L
authors.lastname: Redel
authors.forename: Stella
authors.initials: S
authors.lastname: Suzanne
authors.forename: Carine
authors.initials: C
authors.lastname: Van Lint
authors.forename: Dominique
authors.initials: D
authors.lastname: Lecestre
authors.forename: Sylvette
authors.initials: S
authors.lastname: Chasserot-Golaz
authors.forename: Mark
authors.initials: M
authors.lastname: Leid
authors.forename: Dominique
authors.initials: D
authors.lastname: Aunis
authors.forename: Evelyne
authors.initials: E
authors.lastname: Schaeffer
authors.forename: Olivier
authors.initials: O
authors.lastname: Rohr
mesh_terms: D051836:COUP Transcription Factors; D002352:Carrier Proteins / Q000502:physiology; D002460:Cell Line; D022003:Cell Nucleus Structures / Q000737:chemistry; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D015967:Gene Expression Regulation, Viral; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D017628:Microglia / Q000378:metabolism / Q000821:virology*; D009687:Nuclear Proteins / Q000502:physiology; D017434:Protein Structure, Tertiary; D011987:Receptors, Steroid / Q000032:analysis / Q000037:antagonists & inhibitors / Q000737:chemistry; D012097:Repressor Proteins / Q000032:analysis / Q000502:physiology*; D016329:Sp1 Transcription Factor / Q000032:analysis / Q000037:antagonists & inhibitors / Q000737:chemistry; D014157:Transcription Factors / Q000032:analysis / Q000037:antagonists & inhibitors / Q000737:chemistry; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins; D014779:Virus Replication
chemical_list: C486563:BCL11A protein, human; C479740:BCL11B protein, human; C000715594:CBX5 protein, human; D051836:COUP Transcription Factors; D002352:Carrier Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011987:Receptors, Steroid; D012097:Repressor Proteins; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000090266:Chromobox Protein Homolog 5