Both the folate cycle and betaine‐homocysteine methyltransferase contribute methyl groups for DNA methylation in mouse blastocysts
Bibliographic record
Abstract
The embryonic pattern of global DNA methylation is first established in the inner cell mass (ICM) of the mouse blastocyst. The methyl donor S ‐adenosylmethionine (SAM) is produced in most cells through the folate cycle, but only a few cell types generate SAM from betaine ( N,N,N ‐trimethylglycine) via betaine‐homocysteine methyltransferase (BHMT)' which is expressed in the mouse ICM. Here, mean ICM cell numbers decreased from 18‐19 in controls to 11‐13 when the folate cycle was inhibited by the antifolate methotrexate and to 12‐14 when BHMT expression was knocked down by antisense morpholinos. Inhibiting both pathways, however, much more severely affected ICM development (7‐8 cells). Total SAM levels in mouse blastocysts decreased significantly only when both pathways were inhibited (from 3.1 to 1.6 pmol/100 blastocysts). DNA methylation, detected as 5‐methylcytosine (5‐MeC) immunofluorescence in isolated ICMs, was minimally affected by inhibition of either pathway alone but decreased by at least 45‐55% when both BHMT and the folate cycle were inhibited simultaneously. Effects on cell numbers and 5‐MeC levels in the ICM were completely rescued by methionine (immediate SAM precursor) or SAM. Both the folate cycle and betaine/BHMT appear to contribute to a methyl pool required for normal ICM development and establishing initial embryonic DNA methylation.—Zhang, B., Denomme, M.M., White, C. R., Leung, K.‐Y., Lee, M. B., Greene, N. D. E. Mann, M. R. W. Trasler, J. M., Baltz, J. M., Both the folate cycle and betaine‐homocysteine methyltransferase contribute methyl groups for DNA methylation in mouse blastocysts. FASEB J. 29, 1069–1079 (2015). www.fasebj.org
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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 | 0.006 | 0.001 |
| 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) | 0.000 | 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".