Activator (genetics)

A transcriptional activator is a protein (transcription factor) that increases transcription of a gene or set of genes. Activators are considered to have positive control over gene expression, as they function to promote gene transcription and, in some cases, are required for the transcription of genes to occur. Most activators are DNA-binding proteins that bind to enhancers or promoter-proximal elements. The DNA site bound by the activator is referred to as an "activator-binding site". The part of the activator that makes protein–protein interactions with the general transcription machinery is referred to as an "activating region" or "activation domain".

Most activators function by binding sequence-specifically to a regulatory DNA site located near a promoter and making protein–protein interactions with the general transcription machinery (RNA polymerase and general transcription factors), thereby facilitating the binding of the general transcription machinery to the promoter. Other activators help promote gene transcription by triggering RNA polymerase to release from the promoter and proceed along the DNA. At times, RNA polymerase can pause shortly after leaving the promoter; activators also function to allow these "stalled" RNA polymerases to continue transcription.

The activity of activators can be regulated. Some activators have an allosteric site and can only function when a certain molecule binds to this site, essentially turning the activator on. Post-translational modifications to activators can also regulate activity, increasing or decreasing activity depending on the type of modification and activator being modified.

In some cells, usually eukaryotes, multiple activators can bind to the binding-site; these activators tend to bind cooperatively and interact synergistically.

Activator proteins consist of two main domains: a DNA-binding domain that binds to a DNA sequence specific to the activator, and an activation domain that functions to increase gene transcription by interacting with other molecules. Activator DNA-binding domains come in a variety of conformations, including the helix-turn-helix, zinc finger, and leucine zipper among others. These DNA-binding domains are specific to a certain DNA sequence, allowing activators to turn on only certain genes. Activation domains also come in a variety of types that are categorized based on the domain's amino acid sequence, including alanine-rich, glutamine-rich, and acidic domains. These domains are not as specific, and tend to interact with a variety of target molecules.

Activators can also have allosteric sites that are responsible for turning the activators themselves on and off.

Within the grooves of the DNA double helix, functional groups of the base pairs are exposed. The sequence of the DNA thus creates a unique pattern of surface features, including areas of possible hydrogen bonding, ionic bonding, as well as hydrophobic interactions. Activators also have unique sequences of amino acids with side chains that are able to interact with the functional groups in DNA. Thus, the pattern of amino acid side chains making up an activator protein will be complementary to the surface features of the specific DNA regulatory sequence it was designed to bind to. The complementary interactions between the amino acids of the activator protein and the functional groups of the DNA create an "exact-fit" specificity between the activator and its regulatory DNA sequence.

Most activators bind to the major grooves of the double helix, as these areas tend to be wider, but there are some that will bind to the minor grooves.