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Retrovirology. 2017 Jul 28;14(1):39. doi: 10.1186/s12977-017-0363-4.

Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integration.

Author information

1
Fundamental Microbiology and Pathogenicity Laboratory, UMR 5234 CNRS, University of Bordeaux, SFR TransBioMed, 146 rue Léo Saignat, 33076, Bordeaux Cedex, France.
2
International Associated Laboratory (LIA) of Microbiology and Immunology, CNRS/University de Bordeaux/Heinrich Pette Institute-Leibniz Institute for Experimental Virology, Bordeaux, France.
3
Viral DNA Integration and Chromatin Dynamics Network (DyNAVir), Paris, France.
4
Centre Génomique fonctionnelle Bordeaux, Plateforme Proteome, Université de Bordeaux, Bordeaux, France.
5
Department of Biological Sciences, University of Texas at El Paso, El Paso, TX, USA.
6
Département de Biologie Structurale Intégrative, UDS, U596 INSERM, UMR7104 CNRS, IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), Illkirch-Graffenstaden, France.
7
LBPA, UMR8113, CNRS, ENS-Cachan, Cachan, France.
8
Department of Virology, UMR 3569, CNRS, Institut Pasteur, Paris, France.
9
Institut Cochin-INSERM U1016-CNRS UMR8104, Université Paris Descartes, Paris, France.
10
Fundamental Microbiology and Pathogenicity Laboratory, UMR 5234 CNRS, University of Bordeaux, SFR TransBioMed, 146 rue Léo Saignat, 33076, Bordeaux Cedex, France. vincent.parissi@u-bordeaux.fr.
11
International Associated Laboratory (LIA) of Microbiology and Immunology, CNRS/University de Bordeaux/Heinrich Pette Institute-Leibniz Institute for Experimental Virology, Bordeaux, France. vincent.parissi@u-bordeaux.fr.
12
Viral DNA Integration and Chromatin Dynamics Network (DyNAVir), Paris, France. vincent.parissi@u-bordeaux.fr.

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.

KEYWORDS:

Chromatin; FACT; HIV-1; Integrase; Nucleosome; Retroviral integration

PMID:
28754126
PMCID:
PMC5534098
DOI:
10.1186/s12977-017-0363-4
[Indexed for MEDLINE]
Free PMC Article

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