Structure, Function, and Regulation of TATA Binding Protein Dimers

  • Pugh, Frank (PI)

Project: Research project

Project Details


9808850 Pugh The goal of this project is to address the physiological relevance of the self-association of the TATA binding protein (TBP). Evidence thus far indicates that TBP and TFIID dimerize, whether in vitro or in vivo. Dimerization and DNA binding are competitive reactions. Therefore, the first and foremost priority is to mutagenize the crystallographic dimer interface so as to assess whether the dimer solution structure and the crystallographic structure are congruent. An initial set of mutations is confirming this notion. If dimerization prevents promoter binding by TBP and as a consequence transcription, then the dimer hypothesis predicts that dimer defective TBP mutants should support elevated levels of basal transcription relative to wild type TBP. If activators directly or indirectly facilitate dimer dissociation, then these mutants should not generate elevated levels of activated transcription relative to wild type TBP. Genetic selections will be used to isolate TBP mutants that elevate basal transcription in yeast. Results so far indicate a strong correlation between dimer instability and elevated basal (but not activated) transcription in yeast. The most compelling test for the relevance of TBP dimerization in controlling gene expression will be to isolate second-site intragenic suppressors of the primary mutation and evaluate whether such mutations restore dimer stability and map to the dimer interface that is complementary to the primary mutation. Understanding how each of our -75,000 genes is turned 'on' or 'off' in response to cellular and environmental cues, will lead to a greater understanding of how organisms develop and respond to changing environments. This project is directed at elucidating a potential molecular mechanism by which genes are generally in the 'off' state. Whatever is causing the 'off' state is likely to be the target of gene activators.

Effective start/end date1/1/9912/31/01


  • National Science Foundation: $208,000.00


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