Transcription preinitiation complex

The minimal PIC includes RNA polymerase II and six general transcription factors: TF_IIA, TF_IIB, TF_IID, TF_IIE, TF_IIF, and TF_IIH. Additional regulatory complexes (such as the mediator coactivator and chromatin remodeling complexes) may also be components of the PIC.

Preinitiation complexes are also formed during RNA Polymerase I and RNA Polymerase III transcription.

Assembly (RNA Polymerase II)

A classical view of PIC formation at the promoter involves the following steps:

• TATA binding protein (TBP, a subunit of TFIID) binds the promoter, creating a sharp bend in the promoter DNA.
  • Animals have some TBP-related factors (TRF; TBPL1/TBPL2). They can replace TBP in some special contexts.
• TBP recruits TFIIA, then TFIIB, to the promoter.
• TFIIB recruits RNA polymerase II and TFIIF to the promoter.
• TFIIE joins the growing complex and recruits TFIIH which has protein kinase activity (phosphorylates RNA polymerase II within the CTD) and DNA helicase activity (unwinds DNA at promoter). It also recruits nucleotide-excision repair proteins.
• Subunits within TFIIH that have ATPase and helicase activity create negative superhelical tension in the DNA.
• Negative superhelical tension causes approximately one turn of DNA to unwind and form the transcription bubble.
• The template strand of the transcription bubble engages with the RNA polymerase II active site.
• RNA synthesis begins.
• After synthesis of ~10 nucleotides of RNA, and an obligatory phase of several abortive transcription cycles, RNA polymerase II escapes the promoter region to transcribe the remainder of the gene.

An alternative hypothesis of PIC assembly postulates the recruitment of a pre-assembled "RNA polymerase II holoenzyme" directly to the promoter (composed of all, or nearly all GTFs and RNA polymerase II and regulatory complexes), in a manner similar to the bacterial RNA polymerase (RNAP).