| RRC ID |
77244
|
| 著者 |
Lin J, Ye Y, Shang X, Zhang Y, Wei X, Xu X.
|
| タイトル |
TEA domain transcription factor 4 modulates repression of fetal haemoglobin by direct binding to the γ-globin gene promoters.
|
| ジャーナル |
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.
|
| 巻・号 |
195(5)
|
| ページ |
764-769
|
| 公開日 |
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
|
| リソース情報 |
| ヒト・動物細胞 |
HUDEP-2(RCB4557) |
