This proposal should provide new fundamental insights into the molecular mechanisms of HIV-1 transcriptional latency and reactivation from latency. Overall, this proposal will provide fundamental new insights into the molecular mechanisms of HIV-1 transcriptional latency and reactivation from latency and ultimately should contribute to an increased understanding of AIDS pathogenesis. These aspects of HIV-1 biology might define new potential strategies to purge the latent cellular reservoirs, which constitute today the major hurdle to HIV-1 eradication. Additionally, since chromatin influences the transcriptional regulation of many genes besides HIV-1 the observations made in the HIV system will bear relevance to other human diseases, in which the expression of genes is similarly altered.