Post-fertilization transcription initiation in an ancestral LTR retrotransposon drives lineage-specific genomic imprinting of ZDBF2
Bibliographic record
Abstract
Abstract The imprinted ZDBF2 gene is controlled by oocyte-derived DNA methylation, but its regulatory system is quite different from that of other canonically imprinted genes that are dependent on DNA methylation deposited in the gametes. At the ZDBF2 locus, maternal DNA methylation in the imprinted differentially methylated region (DMR) does not persist after implantation. Instead, a transient transcript expressed in the early embryo exclusively from the unmethylated paternal allele of the DMR, known as GPR1-AS, contributes to establishing secondary DMRs that maintain paternal expression of ZDBF2 in the somatic lineage. While the imprinting of ZDBF2 and its unique regulatory system are evident in humans and mice, whether this process is conserved in other mammals has not been addressed. Here, we show that the first exon of human GPR1-AS overlaps with that of a long terminal repeat (LTR) belonging to the MER21C subfamily of retrotransposons. Although this LTR family appears and is amplified in eutherians, the MER21C insertion into the GPR1-AS orthologous region occurred specifically in the common ancestor of Euarchontoglires, a clade that includes primates, rodents, and rabbits. Directional RNA sequencing of placental tissues from various mammalian species revealed GPR1-AS orthologs in rabbits and nonhuman primates, with their first exon embedded within the same ancestral LTR. In contrast, allele-specific expression profiling showed that cow and tammar wallaby, mammals outside the Euarchontoglires group, expressed both alleles in all tissues analyzed. Our previous studies showed that LTRs reactivated in oocytes drive lineage-specific imprinting during mammalian evolution. The data presented here suggest that LTR-derived sequence activation after fertilization can also contribute to the lineage-specific establishment of imprinted genes.
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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 | 0.000 | 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) | 0.001 | 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".