GATA zinc finger domain-containing protein 2A (GATAD2A) deficiency reactivates fetal haemoglobin in patients with ß-thalassaemia through impaired formation of methyl-binding domain protein 2 (MBD2)-containing nucleosome remodelling and deacetylation (NuRD) complex.
Br J Haematol
; 193(6): 1220-1227, 2021 06.
Article
em En
| MEDLINE
| ID: mdl-33997955
ABSTRACT
Reactivation of fetal haemoglobin (HbF) expression is an effective way to treat ß-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 ß-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 ß-thalassaemia.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
Hemoglobina Fetal
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Nucleossomos
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Células Precursoras Eritroides
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Talassemia beta
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Proteínas de Ligação a DNA
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Complexo Mi-2 de Remodelação de Nucleossomo e Desacetilase
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
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Child
/
Humans
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Male
Idioma:
En
Revista:
Br J Haematol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China