Activator (genetics)

An activator is a DNA-binding protein that regulates one or more genes by increasing the rate of transcription. The activator may increase transcription by virtue of a connected domain which assists in the formation of the RNA polymerase holoenzyme, or may operate through a coactivator. A coactivator binds the DNA-binding activator and contains the domain assisting holoenzyme formation. A particular activator may bind one or more specific coactivators.

Role in Transcriptional Regulation
RNA polymerase (RNAP) is usually bound to the promotor region on the gene which creates a complex that sometimes undergoes a transition that allows transcription to take place. An activator essentially recruits the RNAP to its promotor region, by binding to the activator binding site itself which serves as a liaison between the RNA polymerase and the DNA. Sometimes, the activator is actually required for the RNA polymerase to transcribe DNA by changing its conformation through allostery. In this case, RNAP does not spontaneously transform into the open complex and requires the activator.

Examples
In the lac operon of the bacteria Escherichia coli, the Lac repressor is constitutively expressed and always bound to the operator region of the promotor, interfering with the ability of RNAP to bind to the promotor and transcribe the lac operon. In the presence of lactose, the repressor changes conformation and falls off the operator and RNAP is able to bind to the promotor. The activator catabolite activator protein (CAP) behaves in the exact opposite way. Cyclic adenosine monophosphate (cAMP) is present in low levels of glucose, and binds to CAP which changes to an active conformation. Only then, can CAP act as an activator and help recruit RNAP to its binding site.

In other words, for maximum expression of the lac genes, there needs to be a high level of lactose (for the repressor to fall off) and a low level of glucose (for CAP to recruit RNAP) in the cell. Otherwise, either the repressor will bind to the operator (no genes transcribed), or there is no cooperative binding by CAP thus depending on a spontaneous binding of RNAP (low levels of genes transcribed).