Reference - Detail
| RRC ID | 77244 |
|---|---|
| Author | Lin J, Ye Y, Shang X, Zhang Y, Wei X, Xu X. |
| Title | TEA domain transcription factor 4 modulates repression of fetal haemoglobin by direct binding to the γ-globin gene promoters. |
| Journal | Br J Haematol |
| Abstract |
Re-activation of fetal haemoglobin (HbF) has been proved to be an effective strategy for the treatment of β-haemoglobinopathies. In this study, we identified TEA domain transcription factor 4 (TEAD4) as a new potential regulator of HbF by integrating public data sets with quantitative polymerase chain reaction analysis in β-thalassaemia patients. Significant negative correlation was observed between the expression of TEAD4 and HbF levels in β-thalassaemia patients. Functional validations of TEAD4 inhibition in both β-thalassaemia CD34+ cells and HUDEP-2 cells indicated that depletion of TEAD4 led to a significant increase of HbF. Finally, we identified a binding motif of TEAD4 on γ-globin gene promoters; its disruption consistently led to de-repression of HbF. Taken together, these results demonstrate that TEAD4 could act as a transcriptional inhibitor of the γ-globin gene through direct binding on its promoter. Our findings demonstrate a novel role of TEAD4 on the regulation of HbF, which may benefit patients with β-haemoglobinopathies. |
| Volume | 195(5) |
| Pages | 764-769 |
| Published | 2021-12-1 |
| DOI | 10.1111/bjh.17786 |
| PMID | 34569056 |
| MeSH | Cell Line Erythroid Cells / metabolism Fetal Hemoglobin / genetics* Gene Expression Regulation Humans Promoter Regions, Genetic* Protein Binding TEA Domain Transcription Factors / metabolism* beta-Thalassemia / genetics beta-Thalassemia / metabolism gamma-Globins / genetics* |
| IF | 5.518 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | HUDEP-2(RCB4557) |