GATA-1 Utilizes Ikaros and Polycomb Repressive Complex 2 To Suppress <i>Hes1</i> and To Promote Erythropoiesis
Bibliographic record
Abstract
The transcription factor Hairy Enhancer of Split 1 (HES1), a downstream effector of the Notch signaling pathway, is an important regulator of hematopoiesis. Here, we demonstrate that in primary erythroid cells, Hes1 gene expression is transiently repressed around proerythroblast stage of differentiation. Using mouse erythroleukemia cells, we found that the RNA interference (RNAi)-mediated depletion of HES1 enhances erythroid cell differentiation, suggesting that this protein opposes terminal erythroid differentiation. This is also supported by the decreased primary erythroid cell differentiation upon HES1 upregulation in Ikaros-deficient mice. A comprehensive analysis led us to determine that Ikaros favors Hes1 repression in erythroid cells by facilitating recruitment of the master regulator of erythropoiesis GATA-1 alongside FOG-1, which mediates Hes1 repression. GATA-1 is then necessary for the chromatin binding of the NuRD remodeling complex ATPase MI-2, the transcription factor GFI1B, and the histone H3K27 methyltransferase EZH2 along with Polycomb repressive complex 2. We show that EZH2 is required for the transient repression of Hes1 in erythroid cells. In aggregate, our results describe a mechanism whereby GATA-1 utilizes Ikaros and Polycomb repressive complex 2 to promote Hes1 repression as an important step in erythroid cell differentiation.
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How this classification was reachedexpand
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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".