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10.9:

Eukaryotic Transcription Activators

JoVE Core
Molecular Biology
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JoVE Core Molecular Biology
Eukaryotic Transcription Activators

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Transcription activators are proteins that are responsible for allowing RNA polymerase to initiate transcription. They have two essential domains- one that binds to DNA and another one that activates transcription. The DNA-binding domains contain one of several characteristic structural motifs, including common motifs like the helix-turn-helix, zinc finger, and leucine zipper structures.  A helix-turn-helix domain is made up of two alpha helices joined together by an amino-acid chain that represents the turn. One helix is responsible for recognizing the DNA sequence and fits into the major groove. These proteins bind to DNA as dimers.  A zinc finger contains an alpha helix and a two-strand beta sheet held together by a zinc atom. The helix binds to the major groove with the help of two histidines in its amino acid chain.  A leucine zipper is made up of two monomers that interact with each other in the shape of a Y that binds to the DNA. The monomers consist of leucine at every seventh position at the C-terminal end which interacts with the leucine on the opposite monomer. The N-terminal of the monomer which is made up of basic motifs binds to the DNA. The other essential domain in the activator, the transcription activating domain, recruits co-activators, essential proteins that mediate the binding of activators to RNA polymerase. These co-activators promote transcription through several mechanisms, such as histone modification, which results in increased access of the transcriptional machinery to the DNA.   Activators can also send signals via their co-activators to activate RNA polymerase and initiate transcription. In some cases, activators are essential to the elongation of the transcript. Some polymerases pause transcription after a few nucleotides and need the presence of an activator to restart transcription.   Transcription of a single gene can be regulated by several different activators. When more than one activator is involved in the regulation of transcription, they can act synergistically to drastically increase the rate of transcription in comparison to that of individual activators.

10.9:

Eukaryotic Transcription Activators

Transcription activators are proteins that promote the transcription of genes from DNA to RNA. In most cases, these proteins contain two separate domains ‒ a domain that binds to DNA and a domain for activating transcription; however, in some cases, a single domain is responsible for both binding and activation of transcription, as seen in the glucocorticoid receptor and MyoD.

The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These domains are classified into different families and named according to the structural characteristics that enable DNA recognition and binding. Some common types of binding domains include the leucine zipper, zinc finger, and helix-turn-helix motifs. In contrast, domains responsible for gene transcription activation are usually short, simple sequences and are less complex than the binding domains. They are classified by amino acid composition into categories, such as glutamine-rich, proline-rich, and alanine-rich.

Transcription activators aid in the recruitment of various proteins required for transcription such as general transcription factors, RNA polymerase, and co-activators. All these proteins together are known as the pre-initiation complex and depend on transcription activators for their recruitment to the appropriate location.  These activators can bind to a site close to the gene’s promoter or several thousand base pairs away from the gene to carry out their function. In cases where they are bound to a site away from the gene, they rely on the flexibility of the DNA to bend and bring them in proximity to the gene promoter. Transcription activators are also required to continue a transcript’s elongation or the re-initiation of transcription in cases when the process stops midway. Transcription activators are known to act synergistically. The transcription achieved by the action of multiple activators is higher than what would occur as a  sum of  individual factors working separately.

Like other proteins, transcription activators are subject to post-transcriptional modifications. In many cases these modifications help in positive regulation of transcription. For example, acetylation of p53, an activator that regulates genes responsible for tumor suppression, increases its ability to bind to DNA. 

Suggested Reading

  1. Ma, J. (2006). Transcriptional activators and activation mechanisms. In Gene Expression and Regulation (pp. 147-158). Springer, New York, NY.
  2. Green, M. R. (2005). Eukaryotic transcription activation: right on target. Molecular cell, 18(4), 399-402.