Article (Scientific journals)
Recruitment Of Chromatin-Modifying Enzymes By Ctip2 Promotes Hiv-1 Transcriptional Silencing
Marban, C.; Suzanne, S.; Dequiedt, Franck et al.
2007In EMBO Journal, 26 (2), p. 412-423
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Keywords :
HIV; chromatin; transcription; epigenetic; histone; methylation; virus; T-lymphocytes; HDAC
Abstract :
[en] Following entry and reverse transcription, the HIV-1 genome is integrated into the host genome. In contrast to productively infected cells, latently infected cells frequently harbor HIV-1 genomes integrated in heterochromatic structures, allowing persistence of transcriptionally silent proviruses. Microglial cells are the main HIV-1 target cells in the central nervous system and constitute an important reservoir for viral pathogenesis. In the present work, we show that, in microglial cells, the co-repressor COUP-TF interacting protein 2 (CTIP2) recruits a multienzymatic chromatin-modifying complex and establishes a heterochromatic environment at the HIV-1 promoter. We report that CTIP2 recruits histone deacetylase (HDAC)1 and HDAC2 to promote local histone H3 deacetylation at the HIV-1 promoter region. In addition, DNA-bound CTIP2 also associates with the histone methyltransferase SUV39H1, which increases local histone H3 lysine 9 methylation. This allows concomitant recruitment of HP1 proteins to the viral promoter and formation of local heterochromatin, leading to HIV-1 silencing. Altogether, our findings uncover new therapeutic opportunities for purging latent HIV-1 viruses from their cellular reservoirs.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Marban, C.
Suzanne, S.
Dequiedt, Franck  ;  Université de Liège - ULiège > Gembloux Agro-Bio Tech et GIGA-Research
De Walque, S.
Redel, L.
Van Lint, C.
Aunis, D.
Rohr, O.
Language :
English
Title :
Recruitment Of Chromatin-Modifying Enzymes By Ctip2 Promotes Hiv-1 Transcriptional Silencing
Publication date :
2007
Journal title :
EMBO Journal
ISSN :
0261-4189
eISSN :
1460-2075
Publisher :
Wiley-Blackwell, United States
Volume :
26
Issue :
2
Pages :
412-423
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
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