Transcription factors function to regulate our gene expression to control cell differentiation and how our cells respond to the body's internal and external environment. In order for a gene to be transcribed, certain transcription factors need to be present to activate the DNA transcription machinery. Different transcription factors work to stimulate the transcription of specific genes. During this article, we will discuss common transcription factors and their roles in maintaining bodily homeostasis.
Transcription Factors Definition in Biology
Transcription factors function to turn genes on and off to control which proteins are produced. There are many classes of transcription factors such as activators, repressors, enhancers, silencers, and basal transcription factors.1 Each crucial bodily process is driven by a set of transcription factors responsible for regulating the production of certain cytokines, enzymes, and proteins.1
General Transcription Factors
The human body has a wide array of transcription factors that each function to activate or turn off specific genes. Transcription factors are activated through signal transduction mechanisms within your cells. In other words, after a cell processes a certain signal, usually at the end of a signalling cascade, specific transcription factors can be activated to alter gene expression in response to that signal.
There are many different processes that stimulate the activation of transcription factors. For example, transcription factors are activated when you are ill, when you are asleep, and even when you are sweating.
There is one important class of transcription factors that plays crucial roles in regulating and initiating gene transcription. These general transcription factors are also known as basal transcription factors.1
Transcription factors that are broadly present are called ubiquitous transcription factors.
Basal Transcription Factors
Eukaryotic gene transcription is a complex process regulated by specific promotors and polymerases that need to come together at a certain time and place. To make gene regulation more complex, basal transcription factors, enhancers, and silencers also play roles in regulating the frequency of transcription.1
Enhancers: Specialized transcription factors that increase the rate of transcription.
Enhancers and silencers affect the speed/efficiency of transcription and are not necessary for transcription to occur.1 Basal transcription factors, on the other hand, are vital for the formation of the pre-initiation complex that recruits RNA polymerase II to the DNA template strand.
Transcription is the first step of gene expression where DNA is converted into RNA. Transcription has three steps which are: initiation, elongation, and termination. Transcription initiation is a highly regulated process that involves the activation of many basal transcription factors. These basal transcription factors are needed in order for transcription to occur. We will explore this concept throughout the article.
Basal transcription factor names usually begin with TFII (transcription factor for RNA polymerase II) and are categorized by letters A-J.1 As more proteins and transcription factors migrate to the promoter, each basal transcription factor falls into place on the DNA template to build the pre-initiation complex.
When a eukaryotic cell wants to transcribe a gene many processes must be completed prior to initiating transcription. Transcription factors must first recognize and bind to the promoter region on the DNA template before RNA polymerase II is recruited.
A popular promoter region utilized by the majority of your cells is the TATA box.1 The TATA box serves as the transcription start point.1 Basal transcription factor TFIID recognizes the TATA box region because TFIID has the TATA box binding protein attached to it.1 Once TFIID binds to the TATA box, TFIIB travels to the TATA box and binds to TFIID. The binding of TFIIB attracts RNA polymerase II and TFIIF to bind to the TATA box promoter complex.1 Finally, TFIIE and TFIIH bind to the TATA box as well completing the transcription initiation complex.1 Once the complex is completed, transcription occurs.
Transcription factors that are broadly present are called ubiquitous transcription factors.
Positive Transcription Factor
As we discussed previously, the transcription rate of RNA polymerase II is slow which is why your cells use additional transcription factors known as activators and repressors. Activators and repressors are the cofactors that bind to enhancer and silencer regions of cellular DNA in order to interact with the transcription machinery and influence the rate of transcription.2 Activators serve as positive transcription factors. When an activator binds to a DNA segment for a certain gene, the rate of transcription increases.
An example of an activator is the CAP protein. When cyclic AMP is present, CAP binds to its promoter and increases the transcription activity of RNA polymerase II.5 However, when cyclic AMP is absent, CAP does not bind to the promoter which causes transcription to occur at a slower rate.5 See Figure 2 for an illustration of this phenomenon.
Negative Transcription Factors
Like activators, repressors also influence the rate of transcription. However, repressors function to slow the rate of transcription and are characterized as negative transcription factors.1 Receptors are activated when a cell already has enough of the proteins coded by the gene being transcribed.
For example, when the heat shock factor protein is not present in a cell, the associated repressor does not bind to the operator which allows the transcription machinery to remain active and transcribe the gene needed for the heat shock factor protein. However, when the cell has produced enough heat shock factor protein, the associated repressor is triggered by the abundant levels of heat shock factor in the cell. Once triggered, the repressor binds to the operator and stops transcription of the heat shock factor gene.
Examples of Transcription Factors
Other important transcription factors include enhancers and silencers. Enhancers and silencers are important when some genes need to be expressed or turned off in more than one organ or cell type.2
For instance, suppose you are fighting a virus, and genes associated with apoptosis need to be turned on in the infected cells but not in your healthy cells. This job will require the use of enhancers and repressors. Each enhancer or silencer can activate or repress a gene found only in certain cells or organs.2
Enhancers serve as far-away binding sites for activators, while silencers serve as far-away binding sites for repressors. Both enhancers and silencers have the ability to greatly increase or decrease the transcription of genes in their vicinity.2 Enhancers and repressors can bind thousands of base pairs away from the promoter but still affect the rate of transcription. How is this possible? The short answer is DNA.
Your DNA is a three-dimensional structure that is capable of folding itself many times.2 A given enhancer or promoter may be extremely far away from the promoter of effect; however, if a cell needs to enhance or silence the transcription of a given gene, your DNA will fold itself to bring the enhancer or silencer closer to the target promoter to exert their effects.3 So how do enhancers actually work? Let's discuss this in more detail below.
Apoptosis is the process of programmed cell death. During apoptosis, the cell will essentially self-destruct in response to an intracellular infection, old age, or unrepairable DNA damage. Apoptosis is mediated by a series of intracellular proteins such as P53, and caspases. When the cell has irreversible stress, these proteins will activate causing the cell to self-destruct and die. Apoptosis is necessary to prevent the spread of intracellular pathogens and to reduce inflammation.
In the section discussing basal transcription factors, we discussed the process by which transcription initiation takes place. As all basal factors unite to create the initiation complex, a protein known as a specialized transcription factor binds to an enhancer region upstream of the TATA box promoter.3 Specialized transcription factor (sTF) is special because it can bind with cofactors.3 Cofactors can be either co-repressors or co-activators.3 If the bound cofactor is an activator, the DNA strand will undergo folding to allow the enhancer activator complex to interact with the transcription machinery and thereby regulate the rate of transcription.3
Different Chromatin State of Enhancers and Silencers
As discussed in the regulation of gene expression article DNA within our cells is organized in tightly woven chromatin structures. This arrangement makes DNA inaccessible for transcription. Since enhancers and silencers are regions of DNA, they need to be accessible in order for specialized transcription factors (sTF) and cofactors to bind to it. A given enhancer or silencer can have three different states depending on its level of accessibility within the chromatin.3
Active enhancer/silencer
Primed enhancer/silencer
Closed enhancer/silencer
Transcription Factors - Key takeaways
- Transcription factors are specialized proteins that play key roles in the regulation of gene expression.
- Transcription factors function to turn genes on and off to control which proteins are produced.
- There are many classes of transcription factors such as: activators, repressors, enhancers, silencers, and basal transcription factors.
- Each crucial bodily process is driven by a set of transcription factors responsible for regulating the production of certain cytokines, enzymes, and proteins.
References
- Eggebrecht, J (2018) Biology for AP Courses. Rice University.
- Kolovos, P., Knoch, T.A., Grosveld, F.G. et al. Enhancers and silencers: an integrated and simple model for their function. Epigenetics & Chromatin 5, 1 (2012). https://doi.org/10.1186/1756-8935-5-1
- Animated biology With Arpan (2018) Transcriptional regulation: Enhancers
- Bhatt, D., & Ghosh, S. (2014). Regulation of the NF-κB-Mediated Transcription of Inflammatory Genes. Frontiers in immunology, 5, 71. https://doi.org/10.3389/fimmu.2014.00071
- Biology Libre texts (2021)Catabolite Activator Protein (CAP) - An Activator Regulator
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