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Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integration
- Source :
- Retrovirology, Vol 14, Iss 1, Pp 1-20 (2017), Retrovirology, Retrovirology, 2017, 14 (1), pp.39. ⟨10.1186/s12977-017-0363-4⟩
- Publication Year :
- 2017
- Publisher :
- BMC, 2017.
-
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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 17424690
- Volume :
- 14
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Retrovirology
- Accession number :
- edsair.pmid.dedup....9ec8c2bdc26460a5c28f2a5639693c43
- Full Text :
- https://doi.org/10.1186/s12977-017-0363-4