Genome-wide profiling reveals a dual role for histone H2A monoubiquitylation at Polycomb-repressed and enhancer chromatin
Bibliographic record
Abstract
Abstract Histone modifications are an integral component of eukaryotic genome regulation. Polycomb Repressive Complex 1 (PRC1) is responsible for depositing histone H2A lysine 119 monoubiquitylation (H2AK119ub) and can work cooperatively with PRC2-mediated histone H3 lysine 27 trimethylation (H3K27me3) to maintain gene repression. However, H3K27me3-independent functions and roles in gene activation have also been described for PRC1. Thus, the extent to which Polycomb complexes and their corresponding histone modifications function together or independently and the conservation of these roles in different organisms is unclear. Using C. elegans as a model, we investigated the relationship between H2AK119ub and H3K27me3. Here we show that the majority of H2AK119ub and H3K27me3 enrichment across the genome in embryos is distinct, and that the bulk levels of these modifications are regulated independently. We identify many genes related to nervous system development and functionality that have H2AK119ub-enriched promoters and are misregulated in H2AK119ub-deficient mutants, including a subset of genes that are normally H3K27me3-repressed. Surprisingly, we also find an enrichment of H2AK119ub at enhancers, including enhancers proximal to genes which are both up-regulated and down-regulated following the loss of this histone modification. Together, our results indicate a dual role for H2AK119ub in the regulation of both H3K27me3-repressed and enhancer chromatin states.
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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".