H2A.Z overexpression promotes cellular proliferation of breast cancer cells
Why this work is in the frame
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Bibliographic record
Abstract
We recently showed that histone H2A.Z, as well as members of the ATP-dependent p400 chromatin remodeling complex (p400.com), are essential components of estrogen receptor alpha (ERalpha) signaling. More specifically, we showed that H2A.Z and p400.com are incorporated into the promoter regions of ERalpha target genes only upon gene induction, and also in a cyclic fashion. RNAi-mediated cellular depletion of H2A.Z and p400.com strongly impedes estrogen-dependent growth of breast cancer cells as well as strongly affect ERalpha-target gene expression. Two mechanisms emerged from our studies of how H2A.Z incorporation within ERalpha-target regulatory regions can actually regulate estrogen-mediated signaling: (1) by stabilizing nucleosomes within the translational DNA axis, a process that allows general transcription factors to be efficiently recruited to promoter regions; (2) by allowing estrogen-responsive enhancer function. In the current study, we now show that in MCF7 cells, ectopic overexpression of H2A.Z increases proliferation, and such in conditions where estrogen levels are low. Also, immunohistochemical studies of breast cancer biopsies show that the presence of H2A.Z correlates highly with that of ERalpha, but is associated with high-grade ER-negative cancers. Finally we show that ERalpha directly associates to the H2A.Z promoter, and consequently modulates its expression. Our study provides a possible link between H2A.Z and endocrine resistance by showing that H2A.Z overexpression leads to increased growth, particularly when estrogen levels are very low.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 it