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.
Bertolino
Eric
E
Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA.
Singh
Harinder
H
D000818:Animals; D019556:COS Cells; D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D051863:Host Cell Factor C1; D008958:Models, Molecular; D050811:Octamer Transcription Factor-1; D050809:POU Domain Factors; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D035181:TATA-Box Binding Protein; D035561:Transcription Factor TFIIA; D035581:Transcription Factor TFIIB; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D004268:DNA-Binding Proteins; D051863:Host Cell Factor C1; D050811:Octamer Transcription Factor-1; D050809:POU Domain Factors; D035181:TATA-Box Binding Protein; D035561:Transcription Factor TFIIA; D035581:Transcription Factor TFIIB; D014157:Transcription Factors; D004247:DNA