The enhanceosome

The interferon-beta (IFN-beta) enhanceosome is a paradigm for understanding the role of transcription factor complexes in eukaryotic signal integration. Recent structural studies provide a complete atomic model of the enhanceosome at the protein-DNA interface. The composite model shows how binding of eight transcription factors to enhancer DNA creates a continuous recognition surface. The extensive overlap of individual binding sites creates a composite element that ensures that the enhancer operates as a single unit of regulation. The absence of major protein-protein interfaces between the transcription factors suggests that cooperative binding occurs through a combination of binding-induced conformational changes in DNA structure and specific interactions with coactivator proteins such as CBP/p300. Contacts with virtually every nucleotide explain why the enhancer is evolutionary conserved in mammalian genomes.