The enhanceosome is a protein complex that binds to the "enhancer" region of a gene, found upstream or downstream, of the promoter, or within a gene. It accelerates the gene's transcription. The binding and assembly of the activating proteins, some of which may be transcription factors, is cooperative due to energetically favorable protein-protein interactions formed in the complex.

The best known example of the enhanceosome acts on the human interferon-beta gene, which is upregulated in cells that are infected by viruses. Three activator proteins - NF-kB, an interferon activator protein such as IRF6, and the Jun/ATF complex - cooperatively bind to the upstream enhancer region upon viral infection. The interaction is mediated by a fourth protein HMG-I, which assists in stabilizing the complex by promoting inter-protein interactions. The assembled enhanceosome recruits transcriptional machinery such as RNA polymerase to the promoter region to initiate gene expression.

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