We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Recruitment of chromatin-modifying enzymes by CTIP2 promotes HIV-1 transcriptional silencing.
- Authors
Marban, Céline; Suzanne, Stella; Dequiedt, Franck; de Walque, Stéphane; Redel, Laetitia; Van Lint, Carine; Aunis, Dominique; Rohr, Olivier
- Abstract
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.
- Publication
The EMBO journal, 2007, Vol 26, Issue 2, p412
- ISSN
0261-4189
- Publication type
Journal Article
- DOI
10.1038/sj.emboj.7601516