Figure 2

Functions of CTIP2 in the regulation of HIV-1 gene transcription. CTIP2 (COUP-TF Interacting Protein 2), a transcriptional repressor, has been pointed out as an actor of the latency establishment in the macrophage lineage. First, it has been shown that CTIP2 has a direct impact onto the HIV-1 LTR promoter by replacing transcriptional activator, such P300 (top left). CTIP2 interacts with Sp1, which is anchored to the LTR, switching nuc-1 from a transcriptionally active to a repressive state. Following its binding to Sp1, CTIP2 recruits sequentially histone deacetylase (HDAC) 1 and 2, which remove acetylation marks from the nuc-1 nucleosome, and then SUV39H1, which add a tri-methylation mark onto the lysine 9 of the histone protein H3. As for SUV39H1, it interacts with HP1, a protein stabilizing nuc-1 in a transcriptional closed state. Moreover, CTIP2 is also able to indirectly repress HIV-1 gene transcription. Indeed, CTIP2 can counter the action of the viral protein Vpr. One of the roles of Vpr is to induce a cell cycle arrest through activation of the p21 gene. Sp1-mediated recruitement of Vpr to the p21 gene promoter increases the production of the p21 protein, a cell cycle regulator. Consequence of such block in cell cycle is an enhancement of the viral transcription. The binding of CTIP2 to the p21 promoter forces Vpr release, HDACs and SUV39H1 recruitment, HP1 association and p21 gene silencing.