Figure 3.

Pre-initiation complex formation and promoter proximal stalling. Even under latent conditions, there is an accumulation of RNAPII at the TSS. (A) The binding of host TFs, such as NF-κB and Sp1, and general transcription factors TFIIA, TFIID, and TFIIB to their cognate sites, form the PIC on the HIV-1 promoter. Hypophosphorylated RNAPII is recruited to the PIC through interactions with these TFs. In this state, RNAPII is unable to initiate transcription. (B) The final general transcription factor to be recruited to the PIC is TFIIH. TFIIH binds directly to the DNA and the XPB subunit creates negative supercoiling and serves as a molecular wrench, threading the DNA through the RNAPII active site. The CDK7 subunit of TFIIH phosphorylates Ser7 and Ser5 of the RNAPII C-terminal domain (CTD) to activate the polymerase to begin transcription. (C) Once activated, RNAPII clears the promoter, transcribing the TAR RNA, but pausing just after due to the occlusion by Nuc-1 and the presence of the negative regulators DSIF and NELF. The paused polymerase then dissociates from the DNA and releases the short RNA transcript. RNAPII is then free to participate in PIC formation once again. Thus, there is an accumulation of RNAPII at the promoter of latent proviruses due to both occluded RNAPII in the PIC and stalled polymerases just after the TSS.