Preinitiation complex

The preinitiation complex (abbreviated PIC) is a large complex of proteins that is necessary for the transcription of protein-coding genes in eukaryotes. The preinitiation complex helps position RNA polymerase II over gene transcription start sites, denatures the DNA, and positions the DNA in the RNA polymerase II active site for transcription.

Typically the PIC is made up of six general transcription factors: TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and TFIIH.

In 2007 Roger D. Kornberg proposed the following model of the PIC at promoters with TATA boxes:


 * TATA binding protein (TBP, a subunit of TFIID) binds the promoter, creating a sharp bend in the DNA. This bend wraps the DNA around RNA polymerase II and the C-terminal domain of TFIIB.  TBP binds the TATA box, and the spacing of the TATA box relative to the transcription start site (25-30 base pairs upstream of the transcription start site) ensures that RNA polymerase II will be properly positioned.


 * The N-terminal domain of TFIIB brings the DNA into proper position for entry into the active site of RNA polymerase II.


 * TFIIE joins the growing complex and recruits TFIIH.


 * Subunits within TFIIH that have ATPase and helicase activity create negative superhelical tension in the DNA.


 * Negative superhelical tension causes the DNA to denature and form the transcription bubble. TFIIF binds to the coding strand of the single-stranded, denatured DNA and keeps the bubble open.


 * The single-stranded non-coding strand of the DNA can then bend and enter the RNA polymerase II active site.


 * If transcription proceeds more than six bases, TFIIB is displaced and RNA polymerase II escapes the promoter region to transcribe the remainder of the gene.