Maintenance of germ line and somatic DNA methylation during mouse development
Bibliographic record
Abstract
DNA methylation in mammals is involved in several essential processes including X chromosome inactivation, genomic imprinting, and host defense against mobile genetic elements. How methylation is targeted to specific sequences in the germ line and how specific methylation patterns are maintained during development is not fully understood. Genomic methylation is established in the gamete, decreases dramatically during preimplantation development, and is re-established after implantation of the blastocyst. However, the methylation present at imprinted loci is specifically maintained during preimplantation development. Imprinted genes are located in clusters, and within each gene cluster parent-of-origin specific expression is governed by an imprinting center (IC). The ICs of the maternally imprinted murine Snrpn, Kcnq1, and Igf2r gene clusters coincide with their differentially methylated domains (DMDs). We have shown that specific DMD sequences are required to establish differential methylation at an imprinted locus. Hybrid transgenes were generated using a non-imprinted derivative of the imprinted RSVIgmyc mouse transgene, Ig/myc, and sequences from endogenous imprinted gene DMDs. Addition of specific DMD sequences to the Ig/myc transgene restored its imprinting. Only the tandem repeats found within the Snrpn, Kcnq1, and Igf2r DMDs were capable of establishing maternal-specific transgene methylation. These experiments have also shown that the methylation on imprinted gene DMD sequences is specifically maintained during the early stages of preimplantation development. These results clearly demonstrate the importance of tandem repeats in the process of genomic imprinting. DNA methylation is also critical for silencing intracisternal A particle (IAP) transposition within the genome. It is thought that maintenance of IAP element methylation during preimplantation is critical to repress IAP element transcription and transposition. The methylation of IAP element long terminal repeat (LTR) sequences was analyzed at the blastocyst stage of preimplantation development using the bisulfite genomic sequencing technique. These experiments have shown that methylation is maintained on the majority of IAP elements at the blastocyst stage of preimplantation development. However, the methylation on specific IAP elements is completely lost at this time, including the methylation of single IAP element LTRs.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".