Figure 1.

The HIV promoter is comprised of a series of transcription control elements including NF-kB, Sp1, TATA box, RNA initiation site and the downstream TAR RNA enhancer element. In the presence of Tat, a complex interaction between activators which include NF-kB and/or Sp1 bind to the upstream control region and interact with transcription factors which include, but may not be limited to, TBP, TFIIH, P-TEFb and RNA Pol II. Data from several laboratories now support a role for Tat in transcription complex assembly. Tat and P-TEFb facilitate the binding of TBP to the complex, setting the stage for binding of other basal transcription factors and assembly of the preinitiation complex. In the initiation complex, although both TFIIH and P-TEFb are present, the Pol II CTD is phosphorylated primarily by TFIIH at Ser5 (black). Following synthesis of the TAR RNA enhancer and loss of TFIIH from the elongation complex, P-TEFb is autophosphorylated at Thr186. Transcription elongation requires the interaction of Tat and P-TEFb with the TAR RNA which facilitates the phosphorylation of the Pol II CTD at Ser2 (red) and Ser5 (yellow), as well as the phosphorylation of Tat cofactors Tat-SF1 and SPT5. Whether the Tat and P-TEFb bound to TAR are transferred from the initiation complex, or represent the binding of additional Tat and P-TEFb remains to be established. The Tat-modified kinase activity of P-TEFb is preferentially sensitive to low concentrations of DRB or flavopiridol. This model assumes that the Tat and P-TEFb associated with the initiation complex transfers to the TAR RNA enhancer and perhaps to the elongation complex, a point that has not yet been demonstrated.