YTHDF3 recognizes DNA N6-methyladenine and recruits ALKBH1 for 6mA removal from genomic DNA
Bibliographic record
Abstract
-methyladenine (6mA) is an emerging epigenetic mark in the mammalian genome. ALKBH1 preferentially exhibits 6mA demethylase activity for single-stranded DNA (ssDNA) or bubbled/bulged DNA, but not for double-stranded DNA (dsDNA). Nevertheless, ALKBH1 significantly decreases the cellular 6mA level in genomic DNA, whose prevailing DNA conformation in living mammalian cells is dsDNA. Therefore, the demethylase activity of ALKBH1 toward 6mA in genomic DNA, especially dsDNA, remains largely debated. Here, we found that YTHDF3 increases the 6mA demethylase activity of ALKBH1 in genomic DNA with different conformations, including dsDNA. Compared with ALKBH1, YTHDF3 preferentially recognizes and binds to 6mA-modified DNA with different conformations. YTHDF3 recognizes 6mA in genomic DNA, and binds ALKBH1 to recruit it to sites near 6mA in genomic DNA, thereby facilitating the ALKBH1-mediated removal of 6mA in genomic dsDNA. In summary, YTHDF3 is a novel genomic DNA reader and guides ALKBH1 to remove 6mA in human genomic DNA.
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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 | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".