A coactivator is a protein that increases gene expression by binding to an activator (or transcription factor) which contains a DNA binding domain. The coactivator is unable to bind DNA by itself.^[1][2][3]

The coactivator can enhance transcription initiation by stabilizing the formation of the RNA polymerase holoenzyme enabling faster clearance of the promoter. Coactivators may control many other substeps of transcription, including elongation, RNA splicing, and termination and degradation of the coactivator-activator complex.

Some coactivators possess intrinsic histone acetyltransferase (HAT) activity, which acetylates histones and causes chromatin to relax in a limited region allowing increased access to the DNA. CBP and p300 are examples of coactivators with HAT activity.Numerous other enzyme activities have been reported among the 300 known coactivators for nuclear receptors.^[4] The most well known of these are SRC-1, SRC-2, and SRC-3. Coactivators work in high molecular weight complexes of 6-10 coactivator and coactivator-associated proteins (termed co-coactivators).

The same coactivator will likely be used to increase transcription of many different genes, since it is the activator that provides the specificity to a particular sequence. Recent evidence indicates that coactivators may have diverse roles outside of transcription and that they may act as ‘master genes’ for regulating major cellular and metabolic growth processes.