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  • The EMBO Journal (2007) 26, 412 - 423
  • doi:10.1038/sj.emboj.7601516

Recruitment of chromatin-modifying enzymes by CTIP2 promotes HIV-1 transcriptional silencing

Céline Marban1, Stella Suzanne1,a, Franck Dequiedt2,a, Stéphane de Walque3, Laetitia Redel1, Carine Van Lint3, Dominique Aunis1 and Olivier Rohr1,4

  1. INSERM unité 575 Pathophysiology of Nervous System, Centre de Neurochimie, Strasbourg, France
  2. Cellular and Molecular Biology Unit, Faculty of Agronomy, Gembloux, Belgium
  3. Laboratory of Molecular Virology, Institute for Molecular Biology and Medicine (IBMM) University of Bruxelles (ULB), Gosselies, Belgium
  4. IUT Louis Pasteur de Schiltigheim, Université de Strasbourg, France

Correspondence to:

Olivier Rohr, INSERM unité 575 Pathophysiology of Nervous System, Centre de Neurochimie, 5 rue Blaise Pascal, 67084 Strasbourg, France. Tel.: +33 388 45 66 01; Fax: +33 388 60 07 08; E-mail: rohr@neurochem.u-strasbg.fr

aThese authors contributed equally to this work

Received 27 June 2006; Accepted 29 November 2006

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.

  • Keywords:

    • CTIP2,
    • HDAC,
    • HIV-1,
    • HP1,
    • SUV39H1