GeneID: 494

Description:
GATAD2A, also known as hp66alpha, is a component of the methyl-CpG-binding protein-1 (MeCP1) protein complex, which contains the Mi-2/NuRD complex and two polyptides of 66 and 68 kDa. The Mi-2/NuRD complex contains histone deacetylases and chromatin remodeling factors, and mediates gene repression. It is termed hp66alpha due to its high degree of sequence conservation to the previously identified Xenopus p66 subunit of the Mi-2/NuRD complex. It binds directly to methyl-CpG-binding domain proteins (MBD) within the MeCP1 complex, and enhances MBD2-mediated repression. Efficient repression requires the presence of GATAD2B (hp66beta). MBD2 associates with the Mi-2/NuRD complex, as well as other proteins to mediate transcriptional repression. GATAD2A is known as one of key members of the MBD2-NuRD complex responsible for HbF silencing in adult erythropoiesis. A coiled-coil domain of GATAD2A is indispensable for recruiting CHD4 (Mi-2β) [GeneID: 371] to the MBD2-NuRD complex, which functions as a repressor of gamma-globin genes. CRISPR screens and experimental depletion of GATAD2A in vitro led to reactivation of gamma-globin genes in erythroid cells, primarily by impairing the recruitment of CHD4 to the MBD2-NuRD complex. A naturally occurring mutation in the GATAD2A gene was detected in a patient with Hb E/b0 thalassemia who presented an unexpectedly high level of HbF. GATAD2A is a candidate modifier of disease severity in beta-hemoglobinopathies via modulation of HbF levels.

Synonyms: p66alpha

Comments:
N/A

Number of entries/variants: 1

1. Brackertz M, Boeke J, Zhang R, Renkawitz R, Two highly related p66 proteins comprise a new family of potent transcriptional repressors interacting with MBD2 and MBD3., J Biol Chem, 277(43), 40958-66, 2002 PubMed
2. Sher F, Hossain M, Seruggia D, Schoonenberg VAC, Yao Q, Cifani P, Dassama LMK, Cole MA, Ren C, Vinjamur DS, Macias-Trevino C, Luk K, McGuckin C, Schupp PG, Canver MC, Kurita R, Nakamura Y, Fujiwara Y, Wolfe SA, Pinello L, Maeda T, Kentsis A, Orkin SH, Bauer DE, Rational targeting of a NuRD subcomplex guided by comprehensive in situ mutagenesis., Nat Genet, 51(7), 1149-1159, 2019 PubMed
3. Liang Y, Zhang X, Liu Y, Wang L, Ye Y, Tan X, Pu J, Zhang Q, Bao X, Wei X, Li D, Kurita R, Nakamura Y, Li D, Xu X, 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., Br J Haematol, 193(6), 1220-1227, 2021 PubMed