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.
Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA.
Eric
E
Bertolino
Harinder
H
Singh
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