TEA domain transcription factor 4 modulates repression of fetal haemoglobin by direct binding to the γ‐globin gene promoters
Summary 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 polyme...
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Published in | British journal of haematology Vol. 195; no. 5; pp. 764 - 769 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Blackwell Publishing Ltd
01.12.2021
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Subjects | |
Online Access | Get full text |
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Summary: | Summary
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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0007-1048 1365-2141 |
DOI: | 10.1111/bjh.17786 |