Transcription preinitiation complex

Figure 16 04 01

Transcription Preinitiation Complex (PIC) is a multi-protein structure essential for the transcription of genes in eukaryotic cells. It assembles on the promoter region of a gene before the initiation of transcription. The PIC is crucial for the regulation of gene expression, serving as a platform for the recruitment of RNA polymerase II (Pol II), which is responsible for synthesizing messenger RNA (mRNA) from a DNA template.

Composition

The Transcription Preinitiation Complex comprises several general transcription factors (GTFs) and RNA polymerase II. The core components include:

• TFIIA
• TFIIB
• TFIID, which recognizes and binds to the TATA box in the promoter region through its subunit TBP (TATA-binding protein)
• TFIIE
• TFIIF, which stabilizes the interaction between RNA polymerase II and the TFIIB
• TFIIH, which possesses helicase activity to unwind DNA and kinase activity to phosphorylate the C-terminal domain (CTD) of RNA polymerase II

Function

The assembly of the PIC begins with the binding of TFIID to the promoter region, specifically recognizing the TATA box through its TBP subunit. This is followed by the sequential recruitment of other transcription factors and RNA polymerase II. The formation of the PIC is a highly regulated process, allowing the cell to control gene expression in response to various signals.

Once assembled, TFIIH uses its helicase activity to unwind the DNA, creating a transcription bubble. Its kinase activity then phosphorylates the CTD of RNA polymerase II, triggering the start of transcription. The phosphorylation of the CTD also allows for the recruitment of additional factors necessary for the elongation phase of transcription.

Regulation

The activity and assembly of the PIC can be regulated at multiple levels, including the availability and modification of its components, the presence of transcriptional activators or repressors, and the structure of chromatin. Post-translational modifications of the PIC components, such as phosphorylation, methylation, and acetylation, can influence their activity and interactions, thereby modulating transcription initiation.

Clinical Significance

Dysregulation of the transcription preinitiation complex can lead to aberrant gene expression, contributing to the development of various diseases, including cancer, neurodegenerative diseases, and developmental disorders. Understanding the mechanisms of PIC assembly and function is therefore crucial for developing therapeutic strategies targeting gene expression at the transcriptional level.