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Updated: Jul 17, 2026

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
Recruitment of chromatin-modifying enzymes by CTIP2 promotes HIV-1 transcriptional silencing
Céline Marban1, Stella Suzanne, Franck Dequiedt
1INSERM unité 575 Pathophysiology of Nervous System, Centre de Neurochimie, Strasbourg, France.
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.
Insights
Coup-TF interacting protein 2 (CTIP2) silences latent HIV-1 in microglial cells by forming heterochromatin. This involves recruiting histone deacetylases and methyltransferases, offering potential therapeutic targets for latent HIV-1 reservoirs.
Area of Science:
- Virology
- Epigenetics
- Neuroscience
Background:
- Latent HIV-1 persists in a transcriptionally silent state, often within heterochromatic regions of host genomes.
- Microglial cells are key targets for HIV-1 in the central nervous system and serve as a viral reservoir.
Purpose of the Study:
- To investigate the role of Coup-TF interacting protein 2 (CTIP2) in establishing heterochromatin and silencing HIV-1 in microglial cells.
- To identify the specific molecular mechanisms by which CTIP2 mediates HIV-1 latency.
Main Methods:
- Chromatin immunoprecipitation (ChIP) assays to detect protein-DNA and protein-protein interactions.
- Histone deacetylase (HDAC) and histone methyltransferase activity assays.
- Analysis of histone modifications (acetylation and methylation) at the HIV-1 promoter.
Main Results:
- CTIP2 recruits HDAC1 and HDAC2 to the HIV-1 promoter, leading to histone H3 deacetylation.
- CTIP2 also recruits SUV39H1, a histone methyltransferase, to the HIV-1 promoter, increasing H3 lysine 9 methylation.
- These epigenetic modifications facilitate the formation of heterochromatin via HP1 protein recruitment, resulting in HIV-1 silencing.
Conclusions:
- CTIP2 plays a critical role in establishing heterochromatin at the HIV-1 promoter in microglial cells, contributing to viral latency.
- The recruitment of HDACs and SUV39H1 by CTIP2 are key events in HIV-1 gene silencing.
- Targeting the CTIP2-mediated pathway presents a potential therapeutic strategy for eliminating latent HIV-1 reservoirs.
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