transactivators

Transactivators are proteins that increase transcription by binding to DNA sequences such as promoters or enhancers, or by interacting with components of the transcription machinery. In common usage, transactivators are encoded by genes distinct from the genes they regulate, and thus act in trans rather than in cis.

Most transactivators contain a DNA-binding domain, which recognizes specific DNA motifs, and an activation domain, which recruits coactivators, the Mediator complex, and RNA polymerase II, and may modify chromatin to promote transcription initiation. They can function at promoters directly or at distal regulatory elements through DNA looping. Activity is often regulated by signaling pathways, ligand binding, phosphorylation, or proteolysis.

Examples include GAL4 in yeast, which activates transcription from promoters containing its upstream activating sequence, and bacterial CRP (CAP), which binds near promoters to stimulate RNA polymerase. In mammalian systems, transcription factors such as NF-κB, p53, and steroid hormone receptors act as transactivators. Viral transactivators such as VP16 from herpes simplex virus provide potent activation domains used in engineered constructs (for example, GAL4-VP16).

In synthetic biology and gene therapy, transactivators enable modular control of gene expression. Systems such as Tet-On and Tet-Off use a transactivator protein that responds to doxycycline to regulate transcription from a tetracycline-responsive promoter.

Distinguishing cis- and trans-control, cis-acting elements are DNA sequences that regulate their own adjacent genes, while trans-acting factors are diffusible proteins that regulate other loci.