Ubiquitylated H2A.Z is associated with diverse types of silenced chromatin including methylated CpG islands and homopurine/homopyrimidine sequences
Bibliographic record
Abstract
ABSTRACT H2A.Z monoubiquitylation has been linked to transcriptional repression, but the molecular details involved remain unclear. To address this, we developed a unique ubiquitylation-dependent auto-biotinylation approach, named H2A.Z-UAB, to purify ubiquitylated H2A.Z (H2A.Zub) mononucleosomes for biochemical and genome-wide analyses. We found that H2A.Zub nucleosomes are enriched for the repressive histone post-translational modification H3K27me3 but depleted of H3K4 methylation and other active transcription-associated modifications. ChIP-seq analyses revealed that H2A.Zub-nucleosomes associate with repressive chromatin states and are mostly enriched at genes with low or no expression. Consistent with the biochemical analyses, H2A.Zub ChIP-seq peaks align with regions depleted of H3K4 methylation, H3K27 acetylation, but enriched for H3K27me3. We further observed a strong correlation between high levels of H2A.Zub and DNA methylation, particularly at methylated CpG-rich islands. Finally, we found that a significant proportion of H2A.Zub peaks correspond to homopurine/homopyrimidine sequences that are generally linked to silenced genes and repressive chromatin. Collectively, these findings suggest that H2A.Z ubiquitylation plays an overarching role in global transcriptional silencing through its association with multiple types of repressive mechanisms. GRAPHICAL ABSTRACT
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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) | 0.002 | 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".