POU/TBP cooperativity: A mechanism for enhancer action from a distance

Enhancers when functioning at a distance cannot effectively stimulate transcription from core promoters. We demonstrate that this is due to the inability of enhancer-bound activators to recruit TBP to a distal TATA box. Surprisingly, binding of a transcriptionally inert Oct-1 POU domain near a core promoter enables an enhancer to function from a distance. POU activity neither requires the coactivator OCA-B nor the interaction of TBP with TFIIA. Instead, the POU domain directly facilitates TBP recruitment to the promoter utilizing a bipartite interaction surface. These results establish that an interaction between the DNA binding domain of an activator and TBP can be used to stimulate transcription. Furthermore, they suggest a mechanism for long-range enhancer function in which a TBP complex is preassembled on a promoter via localized recruitment and then acted upon by distal activators.