ACTIVATION OF INTEGRATED PROVIRUS REQUIRES HISTONE ACETYLTRANSFERASE - P300 AND P CAF ARE COACTIVATORS FOR HIV-1 TAT/

A unique aspect of the retrovirus life cycle is the obligatory integra tion of the provirus into host cell chromosomes. Unlike viruses that d o not integrate, retroviruses must conserve an ability to activate tra nscription from a chromatin context. Human immunodeficiency virus (HIV )-1 encodes an unusual and an unusually potent transcriptional transac tivator, Tat, which binds to a nascent viral leader RNA, TAR. The acti on of Tat has been well studied in various reductive model systems; ho wever, the physiological mechanism through which Tat gains access to c hromatin-associated proviral long terminal repeats (LTRs) is not under stood. We show here that a nuclear histone acetyltransferase activity associates with Tat. Intracellularly, we found that Tat forms a ternar y complex with p300 and P/CAF, two histone acetyltransferases (HATs). A murine cell defect in Tat transactivation of the HIV-1 LTR was linke d to the reduced abundance of p300 and P/CAF. Thus, overexpression of p300 and P/CAF reconstituted Tat transactivation of the HIV-1 LTR in N IH3T3 cells to a level similar to that observed for human cells. By us ing transdominant p300 or P/CAF mutants that lack enzymatic activity, we delineated a requirement for the HAT component from the latter but not the former in Tat function. Finally, we observed that Tat-associat ed HAT is preferentially important for transactivation of integrated, but not unintegrated, HIV-1 LTR.