Abstract #1513: Recruitment of histone acetyltransferase activity by the N-terminal homology domain of Pygopus augments TCF-dependent transcriptional activation
Bibliographic record
Abstract
Pygopus is a core component of the beta-catenin/TCF transcriptional activation complex, hypothesized to augment target gene expression by interpreting and modifying the local histone code. Pygopus is essential for development of the early embryo for both Wnt-dependent and Wnt-independent activity and is also required for breast and epithelial ovarian cancer cell growth. The Pygopus protein consists of two conserved domains: a plant homeo domain (PHD), which interacts with the Legless (lgs) adapter protein linking it to the beta-catenin/TCF complex, and an N-terminal homology domain (NHD). The NHD is essential for transcriptional activity, but evidence is lacking on its interaction with other proteins. We now demonstrate that the interaction of Pygopus with histone acetyltransferase (HAT) family members via specific residues in its N-terminal homology domain (NHD) is required to enhance beta-catenin/TCF mediated transcription. The HAT family member CREB Binding Protein (CBP), a component of the beta-catenin/TCF complex, augmented Pygopus-mediated transcription from both TCF/LEF-specific reporter genes, as well as from DNA-tethered Pygopus. Furthermore, immunoprecipitated Pygopus protein complexes displayed CBP-dependent histone acetyltransferase activity. Our data support a model in which the chromatin relaxation requirement in TCF/beta-catenin-mediated transcriptional activation is fulfilled by recruitment of the histone acetyltransferase CBP by Pygopus. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1513.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.008 | 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".