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GATA zinc finger domain‐containing protein 2A ( GATAD2A ) deficiency reactivates fetal haemoglobin in patients with β‐thalassaemia through impaired formation of methyl‐binding domain protein 2 (MBD2)‐containing nucleosome remodelling and deacetylation (NuRD) complex
Author(s) -
Liang Yunhao,
Zhang Xinhua,
Liu Yongqiong,
Wang Liren,
Ye Yuhua,
Tan Xuemei,
Pu Jiajie,
Zhang Qianqian,
Bao Xiuqin,
Wei Xiaofeng,
Li Dongzhi,
Kurita Ryo,
Nakamura Yukio,
Li Dali,
Xu Xiangmin
Publication year - 2021
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.17511
Subject(s) - zinc finger , haploinsufficiency , fetal hemoglobin , chromodomain , biology , mutation , binding protein , binding domain , fetus , microbiology and biotechnology , genetics , helicase , gene , binding site , transcription factor , pregnancy , rna , phenotype
Summary Reactivation of fetal haemoglobin (HbF) expression is an effective way to treat β‐thalassaemia and sickle cell anaemia. In the present study, we identified a novel GATA zinc finger domain‐containing protein 2A ( GATAD2A ) mutation, which contributed to the elevation of HbF and ameliorated clinical severity in a patient with β‐thalassaemia, by targeted next‐generation sequencing. Knockout of GATAD2A led to a significant induction of HbF in both human umbilical cord blood‐derived erythroid progenitor‐2 (HUDEP‐2) and human cluster of differentiation (CD)34 + cells with a detectable impact on erythroid differentiation. Furthermore, heterozygous knockout of GATAD2A impaired recruitment of chromodomain helicase DNA‐binding protein 4 (CHD4) to the methyl‐binding domain protein 2 (MBD2)‐containing nucleosome remodelling and deacetylation (NuRD) complex. Our present data suggest that mutations causing the haploinsufficiency of GATAD2A might contribute to amelioration of clinical severity in patients with β‐thalassaemia.