Spatiotemporal Expression of DNA Demethylation Enzymes and Histone Demethylases in Bovine Embryos
Bibliographic record
Abstract
Fertilization in bovines causes profound changes in the epigenetic profile that affect both DNA methylation patterns and posttranslational histone modifications. These dynamic changes have a great potential for activating pluripotency genes and unfolding certain chromatin regions to recruit different transcription factors. Surprisingly, while the fundamental function of epigenetic remodeling is well understood, the bases of the process are still unknown. Recent developments in epigenetics suggest a multistep demethylation process that would imply the prior modification of the methylated cytosine or methyl group, followed by a DNA repair mechanism implicating enzymes such as activation-induced cytidine deaminase (AICDA) and ten-eleven translocation (TET) dioxygenase. Their functions seem to differ from one species to the other, and they are not yet well characterized in large mammals. Histones have, for their part, many associated and specific lysine demethylases (KDM). Their expression profile in large mammals is not well characterized. We have been interested in characterizing the spatiotemporal expression profile for each of the genes studied to increase our understanding of the molecular interactions following fertilization in early bovine embryo stages. Bovine oocytes and embryos at various preimplantation stages were collected following in vitro fertilization protocol. Total RNA for AICDA, TET1, TET2, TET3, KDM3A, KDM4A, KDM4C, and KDM5B was extracted, reverse transcribed into cDNA, and amplified by real-time PCR. Other embryo pools were collected, and protein localization of the genes studied was characterized. TET3 dioxygenase was present in the very first embryo stages, in contrast to TET1 and AICDA. Histone demethylases KDM3A, KDM4A, and KDM4C were expressed before and after embryonic genome activation, whereas KDM5B was mainly expressed during the blastocyst period. DNA demethylation following fertilization in bovines is not accomplished by AICDA but most probably by TET3. Histone demethylation is carried out by, among others, KDM3A, KDM4A, and KDM4C, which could act in sequence to demethylate histones prior to DNA demethylation of the female chromosomes.
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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) | 0.000 | 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".