T.11 El complejo de pre-iniciación (PIC)

Formation of the Pre-initiation Complex (PIC)

• The PIC is formed through a sequential model, where several factors bind to the promoter region of the DNA.
• The process begins with the recognition of the TATA box by TBP (TATA-binding protein) accompanied by the SAGA complex (in SP promoters) or TFIID (in non-TATA promoters).
• TFIID incorporates TBP and TAFs (TBP-associated factors) to bind to the promoter region.
• Not all promoters are recognized directly by TBP; some are recognized by other factors that form TFIIB.
• The PIC is formed through the recruitment of several factors, including TFIIA, TFIIB, TFIIE, TFIIH, and TFIIJ.

Structure of the PIC

• The PIC is a large complex that includes RNA polymerase II, TBP, TFIIA, TFIIB, and TFIIH.
• The DNA is positioned in the center, and the polymerase is located on one side, while the other factors are positioned on the other side.
• The PIC is held together by protein-protein interactions, allowing the polymerase to access the DNA.
• The complex is dynamic, with factors entering and leaving as transcription proceeds.

Initiation of Transcription

• The transition from the PIC to the open complex (OC) involves the unwinding of the DNA and the binding of the polymerase to the template strand.
• This process requires the activity of TFIIH, which has a helicase subunit that unwinds the DNA.
• The polymerase begins transcription by adding nucleotides to the growing RNA chain.
• As transcription proceeds, the polymerase moves along the DNA, and the factors that made up the PIC dissociate and reassociate with the promoter.

Elongation of Transcription

• The transition from the OC to the elongation complex (EC) occurs when the polymerase begins to synthesize RNA at a high rate.
• During elongation, the polymerase moves rapidly along the DNA, and the RNA grows in size.
• The polymerase may encounter obstacles, such as pauses or roadblocks, which can cause it to stall or backtrack.

Regulation of Transcription

• Transcriptional regulation occurs at multiple levels, including the recruitment of general transcription factors, the binding of specific transcription factors, and the modification of chromatin structure.
• Chromatin remodeling complexes, such as the SWI/SNF complex, play a crucial role in accessing the promoter region by reorganizing the nucleosomes.
• These complexes can either relax or compact chromatin, allowing or blocking access to the promoter region.

Chromatin Remodeling Complexes

• Chromatin remodeling complexes are multi-protein complexes that use ATP to reorganize the nucleosomes and facilitate transcription.
• These complexes often have helicase activity and can recognize specific histone modifications, such as acetylation.
• Examples of chromatin remodeling complexes include the SWI/SNF complex, the RSC complex, and the Mi-2/NuRD complex.