Abstract A033: The ING5 epigenetic reader regulates a subset of DNA repair genes to maintain genomic integrity
Bibliographic record
Abstract
Abstract The ING family of epigenetic histone code readers (ING1-5) recognize the H3K4Me3 epigenetic mark to target histone acetyltransferase (HAT) or histone deacetylase (HDAC) complexes to regulate local acetylation levels and affect transcription. We and others have shown that ING5 promotes stem cell character in normal and in cancer stem cells and that loss of ING5 promotes stem cell differentiation. Examination of an ING5 knockout (KO) mouse model showed increased levels of DNA damage in different tissues, and particularly in the male germ line. ING5 mouse embryo fibroblasts (MEFs) also show a >2-fold increase in cells containing gH2AX foci in the absence of exogenous DNA damaging agents. Examining the transcriptomes of ING5 KO and wild-type littermate MEFs indicates that several genes encoding key DNA repair proteins such as those acting in homologous recombination (BRCA1 and BRCA2) and base excision repair (PARP1) are repressed several-fold and ING5 KO MEFs show increased sensitivity to the PARP inhibitor olaparib. Given that ING5 functions to help maintain stem cell character in normal and in cancer stem cells, we propose that ING5 serves a role in maintaining a high level of DNA repair capability in stem cell populations to preserve genomic integrity. Citation Format: Arthur E Dantas, Buthaina Al-Shueili, Mahbod Djamshidi, Karl Riabowol. The ING5 epigenetic reader regulates a subset of DNA repair genes to maintain genomic integrity [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr A033.
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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) | 0.007 | 0.002 |
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".