Transactivation

Transactivation is the process by which a regulatory protein, typically a transcription factor, increases the transcription of a gene. This activation commonly occurs when the protein binds to specific DNA sequences in promoters or enhancers or when it interacts with other transcription factors and coactivators to stimulate RNA polymerase II recruitment and initiation of transcription. Transactivation can be triggered by cellular signals, developmental cues, or viral proteins that alter transcriptional activity.

Mechanisms of transactivation include direct DNA binding by an activator that recognizes response elements, or indirect action through protein–protein interactions that recruit components of the transcriptional machinery. Activated transcription factors can recruit coactivators with histone acetyltransferase activity, remodel chromatin to a more open state, and bridge enhancers to promoters via mediator complexes, thereby enhancing preinitiation complex assembly and transcriptional output.

Transcription factors often contain activation domains, or transactivation domains, responsible for engaging coactivators and other components of the transcriptional machinery. Viral proteins, such as HIV Tat or Epstein–Barr virus proteins, can function as transactivators to boost viral gene expression. Steroid hormone receptors and other ligand-activated factors also act as transactivators when bound by their ligands to regulate target genes.

In research, transactivation is frequently measured with reporter assays that quantify promoter activity in response to a regulatory protein. Clinically, abnormal transactivation can contribute to diseases such as cancer when transcriptional programs become dysregulated. It is distinct from signal transduction in that it refers to the direct activation of transcription rather than the signaling cascade that precedes it.