Dual DNA demethylation mechanisms implement epigenetic memory driven by the pioneer factor PAX7
Bibliographic record
Abstract
Pioneer transcription factors have the unique ability to open chromatin at enhancers to implement new cell fates. They also provide epigenetic memory through demethylation of enhancer DNA, but the underlying mechanisms remain unclear. We now show that the pioneer paired box 7 (PAX7) triggers DNA demethylation using two replication-dependent mechanisms, including direct PAX7 interaction with the E3 ubiquitin-protein ligase (UHRF1)-DNA methyltransferase 1 (DNMT1) complex that is responsible for DNA methylation maintenance. PAX7 binds to UHRF1 and prevents its interaction with DNMT1, thus blocking activation of its enzyme activity. The ten-eleven translocation DNA dioxygenase (TET) DNA demethylases also contribute to the replication-dependent loss of DNA methylation. Thus, PAX7 hijacks UHRF1 to block activation of DNMT1 after replication, leading to loss of DNA methylation by dilution, and the process is assisted by the action of TET demethylases.
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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 | 0.001 |
| Open science | 0.000 | 0.001 |
| 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".