Cac1p and Rrm3p alter the frequency of epigenetic conversions at the telomeres in S.cerevisiae
Bibliographic record
Abstract
An epigenetic conversion is any inheritable change in gene expression due to change in chromatin structure and not to DNA sequence. These conversions are integral for functional and developmental differentiation in humans, as well as for the immune-evasiveness of certain pathogens. On the other hand, untimely epigenetic switches can cause certain psychiatric disorders and cancer. Despite their significance, the underlying mechanisms involved in epigenetic conversions are yet to be elucidated. The subtelomeric regions of Saccharomyces cerevisiae undergo relatively frequent epigenetic shifts, and as a result, display variegated expression phenotypes. This makes the subtelomeric regions an ideal model system for studying epigenetic conversions. Preliminary findings suggest that pausing of the replication fork may be involved in epigenetic switching. As such, I have hypothesized that the pausing of replication forks stimulates epigenetic shifts and the deletion of genes involved in the regulation of paused forks will affect frequency of variegation. I further hypothesized that pausing of RNA polymerase II during transcription could similarly affect the frequency of variegation. In this thesis I have used a newly developed variegation assay to determine the frequency of epigenetic shifts at the telomeres of several S.cerevisiae strains. These strains harbor mutations in genes involved in replication fork and transcription pausing. I show that there was no impact on the frequency of epigenetic conversions in the transcriptional pausing (Δspt4 and Δdst1) and the fork stabilizing (Δtof1) mutants. However, deletion of the paused replication fork resolving helicase RRM3 (Δrrm3) caused a loss of variegation phenotype, similar to the phenotype observed in Δcac1 cells. These findings suggest that there may be a relationship between replication fork pausing and epigenetic conversions, and furthermore allude to a possible shared mechanism between Rrm3p and Cac1p at a paused fork.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".