Chromatin control of HIV-1 gene expression

Upon infection of susceptible cells, the RNA genome of the human immunodefi ciency virus type 1 (HIV-1) is reverse transcribed into double-stranded DNA , which can be subsequently integrated into the cellular genome. After inte gration, the viral long terminal repeat (LTR) promoter is present in a nucl eosome-bound conformation and is transcriptionally silent in the absence of stimulation. Activation of HIV-1 gene expression is concomitant with an ac etylation-dependent rearrangement of the nucleosome positioned at the viral transcription start site. Thus, similar to most cellular genes, the transc riptional state of the integrated HIV-1 provirus is closely linked to histo ne acetylation. This enzymatic activity results from the function of histon e-specific nuclear acetyltransferase (HAT) enzymes. Efficient viral transcr iption is strongly dependent on the virally-encoded Tat protein. The mechan ism by which Tat increases the rate of transcriptional initiation has been recently demonstrated and involves the interaction of Tat with the transcri ptional coactivator p300 and the closely related CREB-binding protein (CBP) , having histone acetyltransferase activity.