Role of noncanonical histone H2A variant, H2A.Z, to maintain proper centromeric transcription and chromosome segregation
Bibliographic record
Abstract
The genome stability of eukaryotic cells is ensured by proper regulation of histones and their variants. H2A.Z, a conserved and essential histone H2A variant, plays a crucial role in this process by regulating various chromatin-related processes such as gene expression, heterochromatin formation, DNA damage repair, and chromosome segregation. It has two isoforms, H2A.Z1 and H2A.Z2, also known as H2AFZ and H2AFV, respectively, which perform both redundant and nonredundant roles in maintaining genome stability. In this study, we investigated the isoform-specific mitotic functions of H2A.Z in HeLa cells. Our studies revealed that the depletion of H2AFV or H2AFZ did not alter the overall cell cycle profile. However, H2AFV depletion significantly increased the formation of micronuclei, indicating defects in chromosome segregation. Additionally, H2AFV depletion led to the accumulation of DNA damage at various nuclear loci including centromeres. Interestingly, we discovered that H2AFV depletion significantly increased centromeric transcription, which may interfere with proper centromere function. Furthermore, we discovered that a mitotic kinase, Aurora B, binds to both H2AFV and H2AFZ, but preferentially to H2AFV. Inhibition of Aurora B activity by hesperadin disrupted proper centromeric transcription but not significantly centromeric localization of H2A.Z. Collectively, these data demonstrated that the H2A.Z isoforms play distinctive regulatory roles in maintaining proper centromeric transcription and DNA repair, ensuring accurate chromosome segregation.
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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".