Abstract 3108: A novel role for hPygo2 in ribosomal RNA transcription.
Bibliographic record
Abstract
Abstract Background: Several ribosomes are required for each translated messenger RNA. During cell growth and division, a significant proportion of cellular resources are devoted to the production of ribosomes, but the epigenetic mechanisms by which cells adjust to this requirement are not fully understood. We have previously demonstrated that human Pygopus 2 (hPygo2) is highly expressed in, and required for the growth of a number of different cancers. hPygo2 functions as a chromatin remodeling protein through direct association with trimethylated Histone H3 at lysine4 (H3K4me3). It is here that hPygo2 likely serves as an adapter to which histone acetyltransferases can bind and promote further chromatin remodeling events required for transcription. We now present evidence that hPygo2 is involved in chromatin remodeling at the ribosomal (r)RNA promoter during proliferative growth of cancer cells. Methods: Immunoprecipitation (IP) and immunofluorescence (IF) was performed in breast (MCF7), ovarian (SKOV3) and cervical (HeLa) cancer cells. siRNAs were designed to specifically deplete hPygo2. For hPygo2 binding to the ribosomal gene promoter, chromatin IPs were used and analyzed by conventional or quantitative (q) PCR. 47S rRNA expression was measured by qPCR or by pulse-chase with either Br-UTP or 3H-uridine. Cell cycle analysis was performed by flow cytometry. Results: We found that hPygo2 interacted with UBF-1 and Treacle, two nucleolar proteins involved in 47S rRNA transcription. hPygo2 co-localized with UBF-1 and Treacle along with newly synthesized de novo rRNA in the nucleoli of cancer cells. hPygo2 was further detected at the ribosomal gene promoter along with core components of the rDNA transcription complex, including RNA polymerase I. Furthermore, hPygo2 was required for Histone H4 acetylation at the rRNA promoter and for transcription of the 47S pre-rRNA. Depletion of hPygo2 was accompanied by activation of the ribosomal stress response, detected by the binding of ribosomal protein L11 to hdm2, thereby inhibiting its E3 ubiquitin ligase activity resulting in p53 dependent growth arrest. Conclusion: Our results suggest that chromatin remodeling function of hPygo2 may serve to augment or maintain 47S pre-rRNA transcription required for ribosome biogenesis in cancer. Citation Format: Phillip G. P. Andrews, Kenneth R. Kao. A novel role for hPygo2 in ribosomal RNA transcription. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3108. doi:10.1158/1538-7445.AM2013-3108
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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 | 0.000 |
| 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) | 0.003 | 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".