Insulator-based loops mediate the spreading of H3K27me3 over distant micro-domains repressing euchromatin genes
Bibliographic record
Abstract
Abstract Background Chromosomes are subdivided spatially to delimit long-range interactions into topologically associating domains (TADs). TADs are often flanked by chromatin insulators and transcription units that may participate in such demarcation. Remarkably, single-cell Drosophila TAD units correspond to dynamic heterochromatin nano-compartments that can self-assemble. The influence of insulators on such dynamic compartmentalization remains unclear. Moreover, to what extent heterochromatin domains are fully compartmentalized away from active genes remains unclear from Drosophila to human. Results Here, we identify H3K27me3 micro-domains genome-wide in Drosophila, which are attributed to the three-dimensional spreading of heterochromatin marks into euchromatin. Whereas depletion of insulator proteins increases H3K27me3 spreading locally, across heterochromatin borders, it concomitantly decreases H3K27me3 levels at distant micro-domains discrete sites. Quantifying long-range interactions suggests that random interactions between heterochromatin TADs and neighbor euchromatin cannot predict the presence of micro-domains, arguing against the hypothesis that they reflect defects in self-folding or in insulating repressive TADs. Rather, micro-domains are predicted by specific long-range interactions with the TAD borders bound by insulator proteins and co-factors required for looping. Accordingly, H3K27me3 spreading to distant sites is impaired by insulator mutants that compromise recruitment of looping co-factors. Both depletions and insulator mutants significantly reduce H3K27me3 micro-domains, deregulating the flanking genes. Conclusions Our data highlight a new regulatory mode of H3K27me3 by insulator-based long-range interactions controlling distant euchromatic 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 | 0.000 |
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".