Single-molecule chromosome tracing reveals a diversity of megabase heterochromatin domains
Bibliographic record
Abstract
Abstract Chromosomes fold into distinct domains that regulate transcription, replication, and repair. Beyond well-characterized TADs and compartments, the diversity of heterochromatin domains remains poorly defined at the sequence level. Using single-molecule tracing of nascent heterochromatin in C. elegans , we identify three classes of megabase-scale domains: (i) sharp-boundary, Condensin I–dependent Topological Associating Domain-like domains (TADLs); (ii) similarly sized, but Condensin-independent, el egans Condensin -Independent D omains (elCIDs); and (iii) weaker, diffuse structures that are abundant in the population. TADLs arise early in development, preceding elCIDs, and both become progressively compacted through H3K9 methylation, which promotes intra- and inter-domain proximity. Condensin mutations disrupt TADLs, yet single molecules can still form domain-like structures, as recapitulated by free polymer simulations. However, these differ markedly in boundary positioning and biophysical properties. Our results uncover previously unrecognized heterochromatin architectures and demonstrate that single-molecule analysis and mutational dissection provide valuable approaches for distinguishing between domain types.
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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".