Characterization of the Mouse Kcnq1ot1 Non-Coding RNA.
Bibliographic record
Abstract
For a small group of important developmental genes, there is preferential silencing of either the maternal or paternal allele during development. This process of preferential expression is called "genomic imprinting." Imprinted genes often cluster in imprinted domains. Interestingly, these imprinting domains are associated with a non-coding RNA (ncRNA) that may regulate imprinted gene expression across the entire domain. Disruptions in imprinting can have severe consequences for growth and development. In humans, this can result in the development of imprinting disorders such as Beckwith-Wiedemann Syndrome (BWS). BWS is an overgrowth disorder caused by loss of maternal methylation at the KCNQ1OT1 gene. This leads to maternal activation of the normally paternally expressed KCNQ1OT1 ncRNA, and loss of expression of eight maternally expressed protein-coding genes. To understand the complex regulation of genomic imprinting, studies are required to determine how early embryos set up a hierarchy of events that will establish imprinting across large chromosomal domains. Because of the association of ncRNAs with imprinting domains, it is important to elucidate their characteristics and modes of action. The goal of this project is to characterize the mouse Kcnq1ot1 ncRNA and its role in imprinted gene regulation, specifically during preimplantation development. Our findings indicate that the Kcnq1ot1 ncRNA terminates at 462 kb from the transcriptional start site and that this length is conserved in various tissues and developmental stages. This suggests that the boundary between the Kcnq1ot1 and H19 domains resides downstream of Th between 463 and 617 kb, extending the Kcnq1ot1 domain boundary to a region between Th and Ins2, instead of between Ascl2 and Ins2 as previously suggested. shRNA and siRNA targeted disruption of the transcript at 43 kb and 461 kb, respectively, suggests that Kcnq1ot1 is one continuous transcript as opposed to having multiple start sites along the length. In addition, the Kcnq1ot1 transcript originates from the imprinting centre (IC), as deletion of the paternal IC, which contains the Kcnq1ot1 promoter, results in loss of amplification along the length of the transcript. Results from the proposed study will lead to a better understanding of the role that long ncRNAs play in establishing and/or maintaining imprinted gene regulation across imprinting domains, as well as their role in human imprinted disorders. (platform)
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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 | 0.001 | 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) | 0.001 | 0.001 |
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".