preinitieringskomplex

The preinitieringskomplex, known in English as the preinitiation complex (PIC), is a multi-protein assembly that enables transcription by RNA polymerase II in eukaryotes. It comprises RNA polymerase II and the general transcription factors TFIIA, TFIIB, TFIID (which includes TBP and TAFs), TFIIF, TFIIE, and TFIIH. The assembly is guided by promoter DNA and often interacts with coactivators and chromatin modifiers to ensure proper initiation.

Assembly is sequential. TFIID first recognizes promoter DNA, frequently via TBP binding to a TATA box or through TBP-independent contacts with promoter elements via TAFs. TFIIA stabilizes the complex, TFIIB helps recruit RNA Pol II–TFIIF, and TFIIE and TFIIH subsequently join. TFIIH uses XPB/XPD helicases to unwind DNA around the transcription start site, and CDK7 phosphorylates the C-terminal domain of Pol II to permit promoter escape and transition into elongation.

Regulation of PIC assembly is dynamic. Transcription activators, coactivators such as Mediator, and chromatin remodelers modulate accessibility and assembly kinetics. Promoter architecture and histone modifications influence PIC formation, while the complex can be reorganized or disassembled as elongation proceeds, with promoter-proximal pausing in some genes.

Significance: The PIC is essential for controlled gene expression in eukaryotes. Defects in its components can disrupt transcription and contribute to disease; the complex also interfaces with larger regulatory networks governing chromatin state and transcriptional responsiveness.