coactivator

A coactivator is a protein or protein complex that increases transcriptional activation by transcription factors but does not bind DNA directly in a sequence-specific manner. Coactivators function by helping transcription factors communicate with the core transcription machinery, by bridging factors to RNA polymerase II, and by modifying chromatin to create a more permissive transcriptional environment.

Coactivators can be broadly categorized as structural or enzymatic. The Mediator complex is a large, multi-subunit coactivator that acts as a bridge between sequence-specific transcription factors and the general transcription machinery. Enzymatic coactivators often carry histone-modifying activities, such as histone acetyltransferases like CBP and p300, which loosen chromatin structure and enhance access to DNA. Other coactivators recruit chromatin remodelers or additional modifying enzymes, coordinating a multi-step process that supports transcription initiation and elongation. The steroid receptor coactivator (SRC/p160) family (NCOA1-3) exemplifies nuclear receptor coactivators that enhance transcription in response to hormonal signals.

Coactivators are recruited to promoters and enhancers by DNA-bound transcription factors and can influence transcription through several mechanisms, including stabilizing the preinitiation complex, promoting histone acetylation or methylation, and facilitating chromatin remodeling. They are regulated by signaling pathways and play roles in development, metabolism, and cellular responses to stimuli. Coactivators are distinct from co-repressors, which suppress transcription by promoting repressive chromatin states and deactivating transcriptional machinery.