Recruitment of chromatin-modifying enzymes by CTIP2 promotes HIV-1 transcriptional silencing
Céline Marban, Stella Suzanne, Franck Dequiedt, Stéphane de Walque, Laetitia Redel, Carine Van Lint, Dominique Aunis, Olivier Rohr, Céline Marban, Stella Suzanne, Franck Dequiedt, Stéphane de Walque, Laetitia Redel, Carine Van Lint, Dominique Aunis, Olivier Rohr
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.
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Source: PubMed