The histone acetyltransferase, hGCN5, interacts with and acetylates the HIV transactivator, Tat

Factor acetyltransferase activity associated with several histone acetyltra nsferases plays a key role in the control of transcription. Here we report that hGCN5, a well known histone acetyltransferase, specifically interacts with and acetylates the human immunodeficiency virus type 1 (HIV-1) transac tivator protein, Tat. The interaction between Tat and hGCN5 is direct and i nvolves the acetyltransferase and the bromodomain regions of hGCN5, as well as a limited region of Tat encompassing the cysteine-rich domain of the pr otein. Tat lysines 50 and 51, target of acetylation by p300/CBP, were also found to be acetylated by hGCN5. The acetylation of these two lysines by p3 00/CBP has been recently shown to stimulate Tat transcriptional activity an d accordingly, we have found that hGCN5 can considerably enhance Tat-depend ent transcription of the HIV-1 long terminal repeat. These data highlight t he importance of the acetylation of lysines 50 and 51 in the function of Ta t, since different histone acetyltransferases involved in distinct signalin g pathways, GCN5 and p300/CBP, converge to acetylate Tat on the same site.