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A role for TBP dimerization in preventing unregulated gene expression.
A J Jackson-Fisher1, C Chitikila, M Mitra
1Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park 16802, USA.
Molecular Cell
|July 8, 1999
Summary
TATA box-binding protein (TBP) dimerization in yeast prevents uncontrolled gene expression and protein degradation. Disrupting TBP dimers leads to increased gene activity and faster protein breakdown.
Area of Science:
- Molecular Biology
- Yeast Genetics
- Gene Regulation
Background:
- The TATA box-binding protein (TBP) is crucial for gene transcription initiation.
- TBP recruitment to promoters is a rate-limiting step in gene expression.
- Understanding TBP's regulatory mechanisms is key to controlling gene activity.
Purpose of the Study:
- To investigate the role of TBP dimerization in regulating its accessibility to DNA.
- To determine how TBP dimerization affects gene expression and protein stability in yeast.
- To explore the potential of TBP mutations in modulating gene transcription.
Main Methods:
- Utilized crystal structure of TBP dimers to design specific point mutations.
- Assessed TBP dimerization in vitro and gene expression changes in vivo.
- Employed chemical cross-linking to detect TBP dimers directly in yeast cells.
- Investigated the effect of wild-type TBP overexpression on dimerization mutants.
Main Results:
- Mutations disrupting the TBP dimer interface impaired dimerization in vitro.
- Dimerization-defective TBP mutants showed increased activator-independent gene expression in vivo.
- Overexpression of wild-type TBP partially rescued the phenotype of dimerization mutants.
- Dimerization-defective TBPs were rapidly degraded in vivo, indicating loss of autorepression and stability.
Conclusions:
- TBP dimerization acts as a negative autoregulatory mechanism, controlling its accessibility to promoter DNA.
- TBP dimerization is essential for preventing unregulated gene expression.
- TBP dimerization also plays a critical role in maintaining TBP protein stability in vivo.
- Targeting TBP dimerization offers a potential strategy for modulating gene expression.
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