Coactivators

Coactivators are proteins that increase transcriptional activity by binding transcription factors and components of the transcriptional machinery, often without binding DNA themselves. They function by bridging sequence-specific transcription factors to RNA polymerase II and the general transcription factors, or by modifying chromatin to make genes more accessible. Coactivators are distinct from corepressors, which repress transcription, and from sequence-specific transcription factors that can activate transcription directly.

Coactivators can be categorized by mechanism: scaffolding or coordinating factors that assemble the transcriptional machinery, enzymes that modify chromatin, and regulatory complexes such as Mediator. Examples include the p160 family (SRC-1/NCOA1, SRC-2/NCOA2, SRC-3/NCOA3), which are nuclear receptor coactivators that recruit histone acetyltransferases such as CBP/p300 and PCAF to hormone-responsive genes. The Mediator complex acts as a coactivator that relays regulatory information from enhancers to RNA polymerase II. Chromatin-modifying coactivators carry histone acetyltransferase activity (CBP/p300, PCAF); others, like CARM1/PRMT4, methylate histones, and SWI/SNF-type chromatin remodeling complexes reposition nucleosomes to facilitate access.

Coactivator action is often regulated by signaling pathways and ligand binding to transcription factors, especially nuclear receptors. The activity and abundance of coactivators influence gene expression programs during development, differentiation, and response to hormones, and dysregulation is associated with diseases such as cancer. The study of coactivators highlights the integration of signaling, chromatin modification, and transcriptional control in eukaryotic gene regulation.