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.