Transcription Factors

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

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 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.

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.

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.

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.

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

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.

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

1. Active enhancer/silencer

   • The enhancer is fully accessible and regulatory transcription factors are bound to it.³

2. Primed enhancer/silencer

   • The enhancer is fully accessible; however, the regulatory transcription factors are NOT bound to it.³

3. Closed enhancer/silencer

   • The enhancer is not accessible and is tightly wound within the chromatin.³