Abstract 993: A high-throughput peptide array screen of H3K9 methyl effectors identifies UHRF1 as an exception to the “phospho/methyl switch.”
Bibliographic record
Abstract
Abstract Increasing evidence suggests that histone post-translational modifications (PTMs) function in combination to regulate the diverse activities associated with chromatin. However, the mechanisms through which multiple histone PTMs influence the association of effector proteins with chromatin is poorly understood. To address this problem, we recently developed a histone peptide array platform containing singly- and multiply-modified histone peptides to examine the binding of chromatin-associated proteins. Using these arrays, we surveyed protein domains that bound methylated H3K9, and uncovered a number of PTM “patterns” that influenced the association with this mark. Interestingly, while most H3K9 methyl binders were ejected by neighboring H3S10 phosphorylation (a PTM enriched in G2/M-phase chromatin), the tandem Tudor domain (TTD) of UHRF1 was insensitive to this known “phospho/methyl switch”. In agreement, structural and biophysical studies confirmed the insensitivity of the UHRF1 TTD to H3S10 phosphorylation. Furthermore, we found that UHRF1 remains bound to chromatin throughout the cell cycle in contrast to HP1, which is ejected from chromatin during mitosis. These results suggest an important role for this ubiquitin ligase during mitosis. Significantly, we further find that the TTD of UHRF1 regulates global DNA methylation, thus definitively linking H3K9me3 binding by UHRF1 to the maintenance of DNA methylation. Taken together, our data suggest that the regulation of DNA methylation by UHRF1 extends beyond S-phase and requires H3K9me3 recognition during mitosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 993. doi:1538-7445.AM2012-993
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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 | 0.001 |
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".