Preinitiation complex


In eukaryotic transcription, the preinitiation complex is a complex of proteins, stabilised by hydrogen-bonding interactions, which together increase the affinity of RNA polymerase for the promoter of the gene to be transcribed. The proteins in this complex denature and unwind DNA, and insert the DNA into the active site of RNA polymerase ready for transcription. In prokaryotes, by contrast, the preinitiation complex is not needed as RNA polymerase binds directly to the promoter sequence (the sigma factor attached to prokaryotic RNA pol scans the DNA for a promoter sequence).

Some eukaryotic promoters contain a conserved nucleotide sequence called the TATA box. To this region, proteins called TATA-binding proteins (TBPs) can bind, and to the TBPs other proteins can also bind. The TBP turns the DNA through a sharp angle so it is correctly oriented for transcription, and TFIID, itself a complex of proteins called TAFs (TBP-associated factors), binds to the TBP. This stage is called the 'commitment stage' and the complex now-formed is the basal preinitiation complex; the proteins bound so far are known as the general transcription factors.

Because the basal preinitiation complex is formed only of weak hydrogen bond interactions, it can easily dissociate. To ensure strong affinity of RNA polymerase for genes that need to be transcribed, further proteins can bind to it, thereby 'anchoring' it further to the promoter region. These proteins generally bind at regions nearby to the TATA box called promoter-proximal elements. Such elements include the CAAT box and GC boxes, which bind proteins (CAT transcription factors, CTFs, and SP1s, respectively) that themselves act as activators and bind to the nearby preinitiation complex via their activation domains. The activator proteins may induce conformational changes in the existing preinitiation complex in order to make transcription more likely. The stability of the preinitiation complex, and thus the frequency of transcription per unit time, may then be further increased by DNA cis-acting elements called enhancers.

Subsequent to all this is promoter clearance: RNA polymerase departs from the preinitiation complex and begins elongation of the RNA transcript.