USP10 deubiquitylates the histone variant H2A.Z and both are required for androgen receptor-mediated gene activation
Bibliographic record
Abstract
H2A.Z, a variant of H2A, is found at the promoters of inducible genes in both yeast and higher eukaryotes. However, its role in transcriptional regulation is complex since it has been reported to function both as a repressor and activator. We have previously found that mono-ubiquitylation of H2A.Z is linked to transcriptional silencing. Here, we provide new evidence linking H2A.Z deubiquitylation to transcription activation. We found that H2A.Z and ubiquitin-specific protease 10 (USP10) are each required for transcriptional activation of the androgen receptor (AR)-regulated PSA and KLK3 genes. USP10 directly deubiquitylates H2A.Z in vitro and in vivo, and reducing USP10 expression in prostate cancer cells results in elevated steady-state levels of mono-ubiquitylated H2A.Z (H2A.Zub1). Moreover, knockdown of USP10 ablates hormone-induced deubiquitylation of chromatin proteins at the AR-regulated genes. Finally, by sequential ChIP assays, we found that H2A.Zub1 is enriched at the PSA and KLK3 regulatory regions, and loss of H2A.Zub1 is associated with transcriptional activation of these genes. Together, these data provide novel insights into how H2A.Z ubiquitylation/deubiquitylation and USP10 function in AR-regulated gene expression.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".