Fig. 9.

Model for FACT action on HIV-1 integration steps. HIV-1 intasomes are targeted to the PolII-transcribed region of the chromatin thanks to the association of IN with LEDGF/p75 and binding to H3K36me3. In these regions the FACT complex and LEDGF/p75 are both enriched owing to the LEDGF/p75 and SSRP1 interaction. Chromatin remodeling mediated by FACT occurring in the vicinity of the targeted region may generate partially dissociated nucleosomes leading to chromatin structures that are preferential substrates for both RNA transcription and HIV-1 integration. FACT action on chromatin at the vicinity of the integration sites may lead to increased accessibility to nucleosomal DNA as well as histone tails. Integration could then occur efficiently on partially dissociated nucleosome or accessible native nucleosome. Further FACT-mediated regulation of the viral genes transcription can then occur. The expected effect of curaxin treatment on HIV-1 and PFV integration is reported on the basis of the drugs effect on FACT chromatin remodeling activity and on the retroviruses preferences for open or compact chromatin structure