Organizational constraints on Ste12 <i>cis</i>‐elements for a pheromone response in <i>Saccharomyces cerevisiae</i>
Bibliographic record
Abstract
Ste12 of Saccharomyces cerevisiae binds to pheromone-response cis-elements (PREs) to regulate several classes of genes. Genes induced by pheromones require multimerization of Ste12 for binding of at least two PREs on responsive promoters. We have systematically examined nucleotides of the consensus PRE for binding of wild-type Ste12 to DNA in vitro, as well as the organizational requirements of PREs to produce a pheromone response in vivo. Ste12 binds as a monomer to a single PRE in vitro, and two PREs upstream of a minimal core promoter cause induction that is proportional to their relative affinity for Ste12 in vitro. Although consensus PREs are arranged in a variety of configurations in the promoters of responsive genes, we find that there are severe constraints with respect to how they can be positioned in an artificial promoter to cause induction. Two closely-spaced PREs can induce transcription in a directly-repeated or tail-to-tail orientation, although PREs separated by at least 40 nucleotides are capable of inducing transcription when oriented in a head-to-head or tail-to-tail configuration. We characterize several examples of promoters that bear multiple consensus PREs or a single PRE in combination with a PRE-like sequence that match these requirements. A significant number of responsive genes appear to possess only a single PRE, or PREs in configurations that would not be expected to enable induction, and we suggest that, for many pheromone-responsive genes, Ste12 must activate transcription by binding to cryptic or sub-optimal sites on DNA, or may require interaction with additional uncharacterized DNA bound factors.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".