preinitiation

Preinitiation is a term used in molecular biology to describe the preparatory steps that precede transcription initiation by RNA polymerase II. It most often denotes the assembly of the preinitiation complex (PIC) at a gene promoter, a multi-protein complex that positions polymerase II and establishes transcription readiness.

Core components of the PIC include RNA polymerase II and the general transcription factors TBP/TFIID, TFIIA, TFIIB, TFIIF, TFIIE, and TFIIH. TBP-containing TFIID recognizes core promoter elements such as the TATA box or related sequences; other promoters rely on TBP-related factors and promoter-specific activators. The mediator complex and chromatin-remodeling factors assist recruitment and promoter accessibility.

During PIC assembly, TFIID binds first, followed by recruitment of TFIIA, TFIIB, and RNA Pol II with TFIIF; TFIIE and TFIIH join to complete the complex. TFIIH provides helicase activity to melt DNA and kinase activity to phosphorylate the RNA Pol II C-terminal domain, enabling promoter escape and transition to productive elongation.

Preinitiation is regulated by transcription factors, promoter architecture, chromatin state, and coactivators, linking signaling pathways to gene expression. Disruptions in PIC formation can impair transcription and are implicated in various diseases; conversely, regulated PIC assembly allows rapid transcriptional responses.

While the term is most often used for eukaryotes, related concepts exist in archaea with a simplified PIC. In bacteria, transcription initiation relies on a sigma factor and promoter recognition without a canonical PIC.