The preinitiation complex (abbreviated PIC) is a large complex of proteins that is necessary for the transcription of protein-coding genes in eukaryotes (+archaea). 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.[1]
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:[2]
- 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.
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