Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integration
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-media...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-07-01
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| Series: | Retrovirology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12977-017-0363-4 |
| _version_ | 1818556987463434240 |
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| author | Julien Matysiak Paul Lesbats Eric Mauro Delphine Lapaillerie Jean-William Dupuy Angelica P. Lopez Mohamed Salah Benleulmi Christina Calmels Marie-Line Andreola Marc Ruff Manuel Llano Olivier Delelis Marc Lavigne Vincent Parissi |
| author_facet | Julien Matysiak Paul Lesbats Eric Mauro Delphine Lapaillerie Jean-William Dupuy Angelica P. Lopez Mohamed Salah Benleulmi Christina Calmels Marie-Line Andreola Marc Ruff Manuel Llano Olivier Delelis Marc Lavigne Vincent Parissi |
| author_sort | Julien Matysiak |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T23:54:16Z |
| format | Article |
| id | doaj.art-f1a02097fd57468eb90eecfd6d8494e1 |
| institution | Directory Open Access Journal |
| issn | 1742-4690 |
| language | English |
| last_indexed | 2024-12-13T23:54:16Z |
| publishDate | 2017-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Retrovirology |
| spelling | doaj.art-f1a02097fd57468eb90eecfd6d8494e12022-12-21T23:26:40ZengBMCRetrovirology1742-46902017-07-0114112010.1186/s12977-017-0363-4Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integrationJulien Matysiak0Paul Lesbats1Eric Mauro2Delphine Lapaillerie3Jean-William Dupuy4Angelica P. Lopez5Mohamed Salah Benleulmi6Christina Calmels7Marie-Line Andreola8Marc Ruff9Manuel Llano10Olivier Delelis11Marc Lavigne12Vincent Parissi13Fundamental Microbiology and Pathogenicity Laboratory, UMR 5234 CNRS, University of Bordeaux, SFR TransBioMedFundamental Microbiology and Pathogenicity Laboratory, UMR 5234 CNRS, University of Bordeaux, SFR TransBioMedFundamental Microbiology and Pathogenicity Laboratory, UMR 5234 CNRS, University of Bordeaux, SFR TransBioMedFundamental Microbiology and Pathogenicity Laboratory, UMR 5234 CNRS, University of Bordeaux, SFR TransBioMedCentre Génomique fonctionnelle Bordeaux, Plateforme Proteome, Université de BordeauxDepartment of Biological Sciences, University of Texas at El PasoFundamental Microbiology and Pathogenicity Laboratory, UMR 5234 CNRS, University of Bordeaux, SFR TransBioMedFundamental Microbiology and Pathogenicity Laboratory, UMR 5234 CNRS, University of Bordeaux, SFR TransBioMedFundamental Microbiology and Pathogenicity Laboratory, UMR 5234 CNRS, University of Bordeaux, SFR TransBioMedDépartement de Biologie Structurale Intégrative, UDS, U596 INSERM, UMR7104 CNRS, IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire)Department of Biological Sciences, University of Texas at El PasoLBPA, UMR8113, CNRS, ENS-CachanDepartment of Virology, UMR 3569, CNRS, Institut PasteurFundamental Microbiology and Pathogenicity Laboratory, UMR 5234 CNRS, University of Bordeaux, SFR TransBioMedAbstract 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.http://link.springer.com/article/10.1186/s12977-017-0363-4Retroviral integrationHIV-1IntegraseChromatinNucleosomeFACT |
| spellingShingle | Julien Matysiak Paul Lesbats Eric Mauro Delphine Lapaillerie Jean-William Dupuy Angelica P. Lopez Mohamed Salah Benleulmi Christina Calmels Marie-Line Andreola Marc Ruff Manuel Llano Olivier Delelis Marc Lavigne Vincent Parissi Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integration Retrovirology Retroviral integration HIV-1 Integrase Chromatin Nucleosome FACT |
| title | Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integration |
| title_full | Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integration |
| title_fullStr | Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integration |
| title_full_unstemmed | Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integration |
| title_short | Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integration |
| title_sort | modulation of chromatin structure by the fact histone chaperone complex regulates hiv 1 integration |
| topic | Retroviral integration HIV-1 Integrase Chromatin Nucleosome FACT |
| url | http://link.springer.com/article/10.1186/s12977-017-0363-4 |
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