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

Autor: Céline Marban, Stéphane de Walque, Carine Van Lint, Dominique Aunis, Olivier Rohr, Laetitia Redel, Stella Suzanne, Franck Dequiedt
Přispěvatelé: Physiopathologie du système nerveux., Université Louis Pasteur - Strasbourg I-IFR37-Institut National de la Santé et de la Recherche Médicale (INSERM), Cellular and Molecular Biology Unit [Gembloux, Belgium], Faculty of Agronomy [Gembloux, Belgium], Laboratory of Molecular Virology [Gosselies, Belgium], Université libre de Bruxelles (ULB)-Institute for Molecular Biology and Medicine [Gosselies, Belgium], IUT Louis Pasteur de Schiltigheim, This work was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM), by grants from the Agence Nationale de Recherches sur le SIDA (ANRS) to OR and from the French Ministry of Research (‘ACI JC 5364’ to OR and doctoral grant to SS) and by a doctoral INSERM/Conseil Régional d’Alsace grant to CM. FD is ‘chercheur qualifié’ at the FNRS. The work in CVL’s laboratory was supported by grants from the ‘Fonds National de la Recherche Scientifique’ (FNRS, Belgium), the Télévie-Program of the FNRS, the ‘Action de Recherche concertée du Ministère de la Communauté Française' (ULB, ARC program no. 04/09-309), the Internationale Brachet Stiftung (IBS), the Région Wallonne-Commission Européenne FEDER (Intergenes Project, Interreg III program), the Theyskens-Mineur Foundation and the ‘Agence Nationale de Recherches sur le SIDA (ANRS, France)’. CVL is ‘Directeur de Recherches’ of the FNRS. SdW is supported by a postdoctoral fellowship from the ‘Re´gion Wallonne’ (Program WALEO2 convention 616295)., univOAK, Archive ouverte
Jazyk: angličtina
Rok vydání: 2007
Předmět:
Transcription
Genetic
Histone Deacetylase 2
Histone Deacetylase 1
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Biology
Virus Replication
Models
Biological
Article
Histone Deacetylases
General Biochemistry
Genetics and Molecular Biology
Histones
03 medical and health sciences
Histone H3
0302 clinical medicine
Histone H2A
Humans
Histone code
Gene Silencing
Protein Methyltransferases
Promoter Regions
Genetic
Molecular Biology
[SDV.BC] Life Sciences [q-bio]/Cellular Biology
Cells
Cultured
030304 developmental biology
Genetics
0303 health sciences
Histone deacetylase 5
General Immunology and Microbiology
Histone deacetylase 2
Tumor Suppressor Proteins
General Neuroscience
Histone-Lysine N-Methyltransferase
Methyltransferases
Histone H3 deacetylation
Chromatin
3. Good health
DNA-Binding Proteins
Repressor Proteins
Histone methyltransferase
HIV-1
Histone Methyltransferases
Histone deacetylase
030217 neurology & neurosurgery
Protein Binding
Zdroj: EMBO Journal
EMBO Journal, EMBO Press, 2007, 26 (2), pp.412-23. ⟨10.1038/sj.emboj.7601516⟩
ISSN: 0261-4189
1460-2075
DOI: 10.1038/sj.emboj.7601516⟩
Popis: 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.
Databáze: OpenAIRE
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