1. Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integration
- Author
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Matysiak, Julien, Lesbats, Paul, Mauro, Eric, Lapaillerie, Delphine, Dupuy, Jean-William, Lopez, Angelica P., Benleulmi, Mohamed Salah, Calmels, Christina, Andreola, Marie-Line, Ruff, Marc, Llano, Manuel, Delelis, Olivier, Lavigne, Marc, Parissi, Vincent, Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Centre Génomique Fonctionnelle Bordeaux [Bordeaux] (CGFB), Institut Polytechnique de Bordeaux-Université de Bordeaux Ségalen [Bordeaux 2], University of Texas [El Paso] (UTEP ), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Virologie (CNRS - UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by the French National Research Agency (ANR, RETROSelect, jcjc2011 program), the French National Research Agency against AIDS (ANRS, AO2016), SIDACTION (AO2016, VIH20160721002), the French Infrastructure for Integrated Structural Biology (FRISBI) ANR-10-INSB-05-01, Instruct, a part of the European Strategy Forum on Research Infrastructures (ESFRI), the Centre National de la Recherche Scientifique (CNRS), the University of Bordeaux., ANR-11-JSV3-0006,RetroSelect,Contrôle cellulaire de la sélectivité de l'intégration rétrovirale(2011), ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), ruff, marc, Jeunes Chercheuses et Jeunes Chercheurs - Contrôle cellulaire de la sélectivité de l'intégration rétrovirale - - RetroSelect2011 - ANR-11-JSV3-0006 - JCJC - VALID, and Infrastructure Française pour la Biologie Structurale Intégrée - - FRISBI2010 - ANR-10-INBS-0005 - INBS - VALID
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lcsh:Immunologic diseases. Allergy ,Virus Integration ,FACT ,Retroviral integration ,HIV Infections ,HIV Integrase ,Integrase ,MESH: Chromatin ,MESH: HIV-1 ,MESH: Nucleosomes ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Humans ,MESH: Protein Binding ,Histone Chaperones ,MESH: Intercellular Signaling Peptides and Proteins ,Cells, Cultured ,[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,MESH: Humans ,Research ,MESH: Host-Pathogen Interactions ,MESH: Chromatin Assembly and Disassembly ,MESH: Histone Chaperones ,MESH: HIV Infections ,Chromatin Assembly and Disassembly ,Chromatin ,Nucleosomes ,Nucleosome ,Host-Pathogen Interactions ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,HIV-1 ,Intercellular Signaling Peptides and Proteins ,MESH: HIV Integrase ,lcsh:RC581-607 ,MESH: Virus Integration ,Protein Binding ,MESH: Cells, Cultured - Abstract
Background Insertion of retroviral genome DNA occurs in the chromatin of the host cell. This step is modulated by chromatin structure as nucleosomes compaction was shown to prevent HIV-1 integration and chromatin remodeling has been reported to affect integration efficiency. LEDGF/p75-mediated targeting of the integration complex toward RNA polymerase II (polII) transcribed regions ensures optimal access to dynamic regions that are suitable for integration. Consequently, we have investigated the involvement of polII-associated factors in the regulation of HIV-1 integration. Results Using a pull down approach coupled with mass spectrometry, we have selected the FACT (FAcilitates Chromatin Transcription) complex as a new potential cofactor of HIV-1 integration. FACT is a histone chaperone complex associated with the polII transcription machinery and recently shown to bind LEDGF/p75. We report here that a tripartite complex can be formed between HIV-1 integrase, LEDGF/p75 and FACT in vitro and in cells. Biochemical analyzes show that FACT-dependent nucleosome disassembly promotes HIV-1 integration into chromatinized templates, and generates highly favored nucleosomal structures in vitro. This effect was found to be amplified by LEDGF/p75. Promotion of this FACT-mediated chromatin remodeling in cells both increases chromatin accessibility and stimulates HIV-1 infectivity and integration. Conclusions Altogether, our data indicate that FACT regulates HIV-1 integration by inducing local nucleosomes dissociation that modulates the functional association between the incoming intasome and the targeted nucleosome. Electronic supplementary material The online version of this article (doi:10.1186/s12977-017-0363-4) contains supplementary material, which is available to authorized users.
- Published
- 2017
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