Figure 5.

Model for CTIP-2-mediated establishment of a heterochromatin environment at the HIV-1 promoter region. (A) CBP recruitment occurs following HIV-1 activation with phobol esters via CTIP-2, which binds to Sp1 binding sites. (B) However, in latent conditions, the corepressor CTIP-2 interacts with the Sp1 transcription factor at three sites in the HIV-1 5'LTR and consequently recruits HDAC-1 and HDAC-2, leading to H3K9 deacetylation in the nuc-1 region. (C) CTIP-2 then recruits the HMT Suv39 h1, which trimethylates H3K9 (a repressive chromatin mark). (D) This latter epigenetic modification allows HP1 binding and polymerization, heterochromatin formation and propagation at least to the nuc-2 region, and in fine the establishment of HIV-1 silencing [202,203]. This mechanism of viral latency can be revoked by different treatment strategies: HDACIs hinder the repressive action of HDACs and specific HMTIs directed against Suv39 h1 could avoid the recruitment of this silencing machinery.