Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jun;193(6):1220-1227.
doi: 10.1111/bjh.17511. Epub 2021 May 17.

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

Yunhao Liang  1   2   3 , Xinhua Zhang  4 , Yongqiong Liu  1   2   3 , Liren Wang  5 , Yuhua Ye  1   2   3 , Xuemei Tan  1   2   3 , Jiajie Pu  1   2   3 , Qianqian Zhang  1   2   3 , Xiuqin Bao  1   2   3 , Xiaofeng Wei  1   2   3 , Dongzhi Li  6 , Ryo Kurita  7 , Yukio Nakamura  8 , Dali Li  5 , Xiangmin Xu  1   2   3
Affiliations

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

Yunhao Liang et al. Br J Haematol. 2021 Jun.

Abstract

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.

Keywords: GATAD2A mutation; HbF; MBD2-NuRD complex; β-thalassaemia.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Yu X, Azzo A, Bilinovich SM, Li X, Dozmorov M, Kurita R, et al. Disruption of the MBD2-NuRD complex but not MBD3-NuRD induces high level HbF expression in human adult erythroid cells. Haematologica. 2019;104:2361-71.
    1. Sher F, Hossain M, Seruggia D, Schoonenberg VA, Yao Q, Cifani P, et al. Rational targeting of a NuRD subcomplex guided by comprehensive in situ mutagenesis. Nat Genet. 2019;51:1149-59.
    1. Gnanapragasam MN, Scarsdale JN, Amaya ML, Webb HD, Desai MA, Walavalkar NM, et al. p66Alpha-MBD2 coiled-coil interaction and recruitment of Mi-2 are critical for globin gene silencing by the MBD2-NuRD complex. Proc Natl Acad Sci USA. 2011;108:7487-92.
    1. Liu D, Zhang X, Yu L, Cai R, Ma X, Zheng C, et al. KLF1 mutations are relatively more common in a thalassemia endemic region and ameliorate the severity of β-thalassemia. Blood. 2014;124:803-11.
    1. Chen D, Zuo Y, Zhang X, Ye Y, Bao X, Huang H, et al. A genetic variant ameliorates β-thalassemia severity by epigenetic-mediated elevation of human fetal haemoglobin expression. Am J Hum Genet. 2017;101:130-8.

Publication types

MeSH terms

LinkOut - more resources