HIV-1 Tat binds TAF(II)250 and represses TAF(II)250-dependent transcription of major histocompatibility class I genes

HIV Tat, a transactivator of viral transcription, represses transcription of major histocompatibility (MHC) class I genes. Repression depends exclusively on the C-terminal domain of Tat, although the mechanism of this repression has not been known. We now show that repression results from the interaction of Tat with the TAF(II)250 component of the general transcription factor, TFIID. The C-terminal domain of Tat binds to a site on TAF(II)250 that overlaps the histone acetyl transferase domain, inhibiting TAF(II)250 histone acetyl transferase activity. Furthermore, promoters repressed by Tat, including the MHC class I promoter, are dependent on TAF(II)250 whereas those that are not repressed by Tat, such as SV40 and MuLV promoters, are independent of functional TAF(II)250. Thus, Tat repression of MHC class I transcription would be one mechanism by which HIV avoids immune surveillance.