Basal transcription factors are proteins that play a foundational role in initiating gene expression. They are the initial set of proteins that assemble at the beginning of nearly every gene in an organism. Their presence is a prerequisite for a cell to read genetic information stored in DNA and convert it into functional molecules like proteins. These factors create the basic machinery necessary for transcription, the first step in turning a gene “on.”
The Essential Role in Gene Activation
Gene expression is the process by which information from a gene is used to synthesize a functional gene product, such as a protein. This begins with transcription, where the DNA sequence of a gene is copied into a messenger RNA (mRNA) molecule. Basal transcription factors are required for this initial copying step for most genes. They act as the machinery that prepares the gene for transcription, enabling RNA polymerase to function.
These factors differ from regulatory transcription factors, which fine-tune gene expression by increasing or decreasing the rate of transcription. While regulatory factors dictate when and how much a gene is expressed, basal transcription factors establish the platform for transcription. Without their assembly, RNA polymerase II, the cellular machinery responsible for copying DNA into RNA, would not be able to bind to the gene and begin its work.
How Basal Transcription Factors Work
Transcription initiation begins with the assembly of basal transcription factors at a specific region of a gene called the promoter. This assembly forms a large protein complex known as the pre-initiation complex (PIC). The first step involves the TATA-binding protein (TBP), a component of the TFIID complex, binding to a specific DNA sequence within the promoter called the TATA box. This binding causes a significant bend in the DNA.
Following TBP’s binding, other basal transcription factors sequentially join the complex. TFIIB binds next, acting as a bridge between TFIID and RNA polymerase II, and helps position RNA polymerase II correctly over the promoter. RNA polymerase II, the enzyme responsible for synthesizing RNA, is then recruited to the promoter along with TFIIF. TFIIF facilitates RNA polymerase II loading and stabilizes TFIIB.
TFIIE and TFIIH subsequently join the growing complex, completing the pre-initiation complex. TFIIE recruits TFIIH. TFIIH plays an important role by unwinding the DNA helix at the promoter to create a “transcription bubble” and chemically modifying RNA polymerase II, preparing it for transcription. Once the PIC is fully assembled and activated, RNA polymerase II can then move along the DNA, synthesizing an RNA molecule that carries the gene’s instructions.
Why They Matter for Life
Basal transcription factors are essential for all forms of life because they are essential for the expression of nearly every gene. Their proper functioning ensures that the cell can produce the proteins and other molecules necessary for its survival and specialized functions. This includes everything from metabolic enzymes that generate energy to structural proteins that maintain cell shape.
The continuous and accurate operation of these factors is also important for maintaining cellular homeostasis, the stable internal environment necessary for cells to function correctly. They are also important for developmental processes, guiding the precise timing and expression of genes that dictate how an organism grows and forms. Any malfunction or disruption in the activity of basal transcription factors can have significant consequences, potentially leading to developmental disorders or various diseases, as cells’ ability to express genes is compromised.