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

Mol Cell. 2002 Aug;10(2):397-407. doi: 10.1016/s1097-2765(02)00597-x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Cell Line
  • DNA / genetics
  • DNA / metabolism*
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism*
  • Electrophoretic Mobility Shift Assay
  • Enhancer Elements, Genetic / genetics*
  • Host Cell Factor C1
  • Models, Molecular
  • Octamer Transcription Factor-1
  • POU Domain Factors
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Protein Structure, Tertiary
  • TATA-Box Binding Protein
  • Transcription Factor TFIIA
  • Transcription Factor TFIIB
  • Transcription Factors / chemistry*
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Transfection

Substances

  • DNA-Binding Proteins
  • Host Cell Factor C1
  • Octamer Transcription Factor-1
  • POU Domain Factors
  • TATA-Box Binding Protein
  • Transcription Factor TFIIA
  • Transcription Factor TFIIB
  • Transcription Factors
  • DNA