Types of Transcriptional Regulators
Transcription factors are proteins that bind to specific DNA sequences and initiate the transcription of a gene. They usually bind to the promoter just upstream of the gene.
There are two main types of transcription factors. These are General or Basal transcription factors and Specific Transcription factors.
Activators promote transcription by binding to specific DNA sequences (the “binding site”) in the genome that is associated with nearby promoters. RNA polymerase then binds to the binding sites and starts transcribing.
Unlike repressors, which are found in the same DNA region as the promoter, activators may be located far away from the promoter and affect transcription at other sites. They’re often part of a loop of DNA that helps bring binding sites for general transcription factors and other proteins near RNA polymerase and the nearby promoter.
Activators are composed of two different parts: the DNA binding domain and the activation domain. In addition to these two parts, activators also have a “business end” that facilitates the formation of the transcription initiation complex at the target DNA sequence.
Repressors are proteins that inhibit the expression of a gene. They typically bind to critical DNA sequences in the gene and block mRNA transcription from that gene.
Repression mechanisms are complex and often involve the interaction of other molecules, such as corepressors and inducers. These molecules can bind to and activate the repressor.
A repressor binds to a specific DNA sequence, which is its binding site (sometimes called a recognition site or an operator). When bound to this sequence, the repressor blocks the formation of a transcription initiation complex at the promoter of a nearby gene.
Repressors can be found in many different parts of DNA and can affect genes that are located at large distances from the ones they affect. They also can be involved in combinatorial regulation, which means that they can affect multiple genes at the same time.
Enhancers are stretches of deoxyribonucleic acid (DNA) that provide binding sites for proteins that help activate transcription, which is the process of making RNA. When these proteins bind to an enhancer, the shape of the DNA changes. This allows the activator to interact with the transcription factors that are bound to the promoter region of a gene, which leads to the production of RNA.
Enhancer function is conserved across hundreds of millions of years of evolution. For example, scientists found that a genetic element from the sea sponge Amphimedon queenslandica can drive transcription in certain cell types in mice and zebrafish even though it doesn’t normally belong to these organisms.
Enhancers contain dense clusters of transcription factor binding sites and are bound by cell type-specific TFs, coregulators, chromatin modifiers, architectural proteins like Cohesin, Condensin, and CTCF, other enzymes, and RNA polymerase II (RNAPII). These factors may be assembled in the enhancer in successive phases of protein recruitment to form enhancer complexes that loop over target promoters.
Silencers are a type of transcriptional regulator. These are elements that repress genes and regulate their expression by binding to TFs in the target gene. These elements are similar to enhancers in their sequence features, but they differ in how they interact with TFs and how they affect transcription.
Silencers are usually identified by their activity in a reporter assay. In this assay, a test sequence that represses expression in the domain of putative silencer activity is included in a vector to identify it.
However, these assays do not always provide a detailed description of the pattern of repression. Depending on the target gene and cellular state, the silencer could repress expression in a stripe orthogonal to the domain, or it could nucleate the spread of heterochromatin from a different region of the genome.
Understanding the cell type and developmental stage specificity of silencer activity, the extent of bifunctionality of cis-regulatory elements, and the chromatin and sequence features of silencers is critical for advancing our understanding of their activities (see Outstanding Questions). A manually curated database of published silencer elements, SilencerDB, is currently being developed.
