Diversity of acetylation targets and roles in transcriptional regulation: the human immunodeficiency virus type 1 promoter as a model system.

Persuasive evidence has accumulated that reversible acetylation of proteins is key post-translational modification regulating transcription in eukaryotes. Deacetylase inhibitors (such as trichostatin A) modulate the expression of approximately 2% of all cellular genes. We and others have demonstrated a marked transcriptional activation of the human immunodeficiency virus type 1 (HIV-1) promoter in response to deacetylase inhibitors. Deacetylation events seem to be an important mechanism of HIV-1 transcriptional repression during latency, whereas acetylation events play critical functional roles in HIV-1 reactivation from latency. These deacetylation/acetylation events are implicated in chromatin remodeling of the viral promoter region, as well as in modulating the functional properties of cellular and viral transcription factors binding to this promoter region. Thereby, the HIV-1 promoter constitutes a unique regulatory model system to study the complex relationship between acetylation processes and transcriptional activity.