Molecular determinants underlying functional divergence of TBP homologs
Bibliographic record
Abstract
Abstract The TATA-box binding protein (TBP) is a highly conserved basal transcription factor and a core component of the pre-initiation complex (PIC) for all three eukaryotic RNA polymerases (RNA Pols). Despite this conservation, TBP function diverges across species. In yeast, TBP is required for all three RNA Pols, whereas in mammals, it is essential only for RNA Pol III, but not RNA Pol I or II. To examine the evolutionary divergence of TBP homologs in different species, we determined the ability of murine TBP and its paralogs to complement endogenous TBP in Saccharomyces cerevisiae . Despite their highly conserved DNA-binding domains, murine TBP homologs were unable to fully rescue the lethality caused by TBP inactivation in yeast. This incomplete complementation correlates with a failure to fully support binding by RNA Pols II and III. Furthermore, we show that the divergent N-terminal domain (NTD) of TBP contributes to species-specific activity and modulates RNA Pol II binding changes in stress-induced response. Lastly, we demonstrate a negative correlation between the length of the intrinsically disordered NTD of TBP family proteins and the gene density in different species, suggesting that the NTD may have contributed to increasingly complex gene regulation during evolution.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".