Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integration
Posted on 2017-07-28 - 05:00
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.
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Matysiak, Julien; Lesbats, Paul; Mauro, Eric; Lapaillerie, Delphine; Dupuy, Jean-William; Lopez, Angelica; et al. (2017). Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integration. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.3838858.v1
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AUTHORS (14)
JM
Julien Matysiak
PL
Paul Lesbats
EM
Eric Mauro
DL
Delphine Lapaillerie
JD
Jean-William Dupuy
AL
Angelica Lopez
MB
Mohamed Benleulmi
CC
Christina Calmels
MA
Marie-Line Andreola
MR
Marc Ruff
ML
Manuel Llano
OD
Olivier Delelis
ML
Marc Lavigne
VP
Vincent Parissi