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Functional divergence of TBP homologs through distinct DNA-binding dynamics
Jieying H Cui1, James Z J Kwan1, Armin Faghihi1
1Department of Biochemistry and Molecular Biology, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BCV6T 1Z3, Canada.
Nucleic Acids Research
|May 21, 2025
Summary
Homologous TATA box-binding proteins (TBPs) are essential for eukaryotic transcription but show species-specific functions. These differences, particularly in RNA Polymerase III support and DNA binding dynamics, explain their varied roles in gene regulation.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- TATA box-binding protein (TBP) is a conserved transcription factor crucial for RNA Polymerases I, II, and III.
- Homologous TBPs display species- and tissue-specific functions, impacting gene expression regulation.
Purpose of the Study:
- To investigate the molecular mechanisms behind species- and tissue-specificity of homologous TBPs.
- To assess the functional replacement of endogenous TBP by yeast and murine TBP paralogs in mouse embryonic stem cells (mESCs).
Main Methods:
- Utilized mouse embryonic stem cells (mESCs) to test the functional rescue of TBP depletion by homologous TBPs.
- Assessed the ability of homologous TBPs to support RNA Polymerase III transcription.
- Analyzed the role of the N-terminal domain in stress-induced transcriptional reprogramming.
- Examined DNA binding dynamics of homologous TBPs.
Main Results:
- Homologous TBPs could not fully rescue TBP depletion lethality in mESCs, correlating with impaired RNA Pol III transcription support.
- The N-terminal domain of homologous TBPs influences transcriptional response during stress.
- Significant differences in DNA binding dynamics were observed among homologous TBPs.
Conclusions:
- Homologous TBPs exhibit a balance of flexibility and essentiality in eukaryotic transcription.
- Species- and tissue-specific functions of TBPs are influenced by their divergent domains and DNA binding kinetics.
- Understanding TBP functional divergence is key to comprehending complex gene expression regulation.
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