COUP-TF interacting protein 2 represses the initial phase of HIV-1 gene transcription in human microglial cells.
Fiche publication
Date publication
janvier 2005
Journal
Nucleic acids research
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CHASSEROT-GOLAZ Sylvette, Pr ROHR Olivier
Tous les auteurs :
Marban C, Redel L, Suzanne S, Van Lint C, Lecestre D, Chasserot-Golaz S, Leid M, Aunis D, Schaeffer E, Rohr O
Lien Pubmed
Résumé
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.
Mots clés
COUP Transcription Factors, Carrier Proteins, physiology, Cell Line, Cell Nucleus Structures, chemistry, Chromosomal Proteins, Non-Histone, analysis, DNA-Binding Proteins, analysis, Gene Expression Regulation, Viral, HIV Long Terminal Repeat, HIV-1, genetics, Humans, Microglia, metabolism, Nuclear Proteins, physiology, Protein Structure, Tertiary, Receptors, Steroid, analysis, Repressor Proteins, analysis, Sp1 Transcription Factor, analysis, Transcription Factors, analysis, Transcription, Genetic, Tumor Suppressor Proteins, Virus Replication
Référence
Nucleic Acids Res.. 2005 ;33(7):2318-31