Identification of an Erythroid Active Element in the Transferrin Receptor Gene
Why this work is in the frame
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Bibliographic record
Abstract
Hemoglobin synthesis consumes most of the iron that is taken up by cells from plasma transferrin, and this process requires very high expression of transferrin receptors (TfR) at the membranes of erythroid cells. Studies in our and other laboratories indicate that a dramatic increase in TfR levels during erythroid differentiation occurs at the transcriptional level. In this study, we investigated the transcriptional regulation of the TfR in terms of its promoter activity and DNA-protein binding in murine erythroleukemia cells. Reporter gene assays revealed that the TfR promoter activity was stimulated 6-8-fold in murine erythroleukemia cells induced to differentiate into hemoglobin-synthesizing cells by either Me(2)SO or N,N'-hexamethylene-bis-acetamide. A minimal region (-118 to +14) was required for the differentiation-induced promoter activity. Mutation of either an Ets-binding site or an activator protein-1/cyclic AMP-response element-like motif within this region, but not disruption of the adjacent GC-rich/specificity protein-1 sequence, inhibited the inducible promoter activity. Electrophoresis mobility shift assays suggest that the cyclic AMP-response element-binding proteins/activating transcription factor-like factors and Ets-like factors bind constitutively to this bipartite element. Upon induction of differentiation, a shift in the pattern of the cyclic AMP-response element-binding protein/activating transcription factor-like binding factors was observed. Our data indicate that the TfR gene promoter contains an erythroid active element that stimulates the receptor gene transcription upon induction of hemoglobin synthesis.
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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) | 0.002 | 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