Fig. 1.

Transcription factors controlling activation and repression of the HIV-1 LTR. a Transcription factors mediating the activation of HIV-1 transcription. The enhancer region of the 5′ HIV-1 LTR binds multiple transcriptional activator proteins [AP1, NF-κB, SP1, NFAT, GABP/Ets, USF1/2/TFII-I (RBF-2)] that recruit general transcription factors and co-activator complexes to stimulate transcription by RNA Polymerase II (Pol II). Transcription of the HIV-1 5′ mRNA region produces the TAR (TAT-Responsive) RNA stem-loop structure that binds the viral TAT protein, which recruits elongation factor pTEFB to inhibit negative regulators of pausing, DSIF and NELF, and promote elongation by RNA Pol II. The 5′ LTR is associated with two strongly positioned nucleosomes, designated nuc-0 and nuc-1; transcriptional activation from the LTR is causes dissociation of nuc-1 near the core promoter. b Factors causing repression of HIV-1 transcription in unstimulated cells. In unstimulated cells, activator proteins are replaced by transcriptional repressors (NF-κB p50, CBF-1) that recruit histone deacetylase and histone methyltransferase complexes. Several LTR-bound factors are converted from activators to repressors (SP1/3 (RBF-2)/TFII-I) that recruit HDAC enzymes (HDAC1/2/3). The multifunctional factor YY1 (Yin Yang 1) is associated with the latent provirus 5′ LTR and also recruits HDACs. Several factors, including CTIP-2, recruit histone methyltransferases (Suv39H1) that promote transcriptional silencing and spreading of repressive chromatin